Transect-based trapping for area-wide delimitation of insects.

Typical delimitation trapping survey designs for area-wide (nonlocalized) insect populations are regularly spaced grids, and alternative shapes have not been evaluated. We hypothesized that transect-based designs could give similar detection rates with significantly shorter servicing distances. We used the TrapGrid model to investigate novel "trap-sect" designs incorporating crossed, spoked, and parallel lines of traps, comparing them to a regular grid, in single survey and multiple-site scenarios. We calculated minimum servicing distances and simulated mean probabilities of detecting a pest population, judging overall performance of trap network designs using both metrics. For single sites, trap-sect designs reduced service distances by 65-89%, and most had similar detection probabilities as the regular grid. Kernel-smoothed intensity plots indicated that the best performing trap-sect designs distributed traps more fully across the area. With multiple sites (3 side by side), results depended on insect dispersal ability. All designs performed similarly in terms of detection for highly mobile insects, suggesting that designs minimizing service distances would be best for such pests. For less mobile pests the best trap-sect designs had 4-6 parallel lines, or 8 spokes, which reduced servicing distances by 33-50%. Comparisons of hypothetical trap-sect arrays to real program trap locations for 2 pests demonstrated that the novel designs reduced both trap numbers and service distances, with little differences in mean nearest trap distance to random pest locations. Trap-sect designs in delimitation surveys could reduce costs and increase program flexibility without harming the ability to detect populations.

Simulation-based evaluation of two insect trapping grids for delimitation surveys.

In the United States of America, delimitation trapping surveys with square grids have been used for decades for exotic insects without rigorous evaluation. We used simulations to investigate the effectiveness of two representative designs: an 8-km grid for Acrolepiopsis assectella (leek moth) and a 14.5-km grid for Ceratitis capitata (Mediterranean fruit fly, "Medfly"). We investigated grid compositions and design factors, measuring performance as the mean probability of pest capture over all traps, p(capture), and designed improved grids for both species. For the standard designs, p(capture) was 0.86 for leek moth and 0.71 for Medfly, with the latter performing better due to greater lure and trap attractiveness. For both designs, 86 percent or more of mean p(capture) came from core area captures. Egress testing indicated that both grids were oversized. An improved grid for leek moths would use 177 traps in a 4.8-km diameter circle, which had mean p(capture) = 0.73 and reduced the cost by 80 percent. The best Medfly grid was a 4.8-km diameter circle with 232 traps, which gave mean p(capture) of 0.66 and reduced the cost by 86 percent. Simulation may be used to improve trapping survey plans, often saving significantly on costs while maintaining survey performance.

Simulation-Based Investigation of the Performance of Delimiting Trapping Surveys for Insect Pests.

Fully trapped survey designs are widely used to delimit adventive pests populations that can be detected using traps and lures. Delimitation includes verifying the presence of the pest and determining its spatial extent. The size and shape of the survey design and the density of traps can vary; however, resulting variation in detecting efficiency is often unknown. We used a trapping network simulation model with diffusion-based insect movement to investigate delimiting survey trapping design performance for fully trapped and some modified designs. Simulations included randomized outbreak locations in a core area and a duration of 30 d. We assessed impacts of insect dispersal ability, grid size and shape, and trap attractiveness and density on survey performance, measured as mean probability of capturing individual pests [p(capture)]. Most published grids are square, but circles performed equally well and are more efficient. Over different grid sizes, p(capture) increased for insects with greater dispersal ability but was generally unresponsive to size because most captures occurred in central areas. For low dispersing insects, the likelihood of egress was approximately zero with a 3.2-km square grid, whereas an 11.3-km grid was needed to contain highly vagile insects. Trap attractiveness affected p(capture) more strongly than density: lower densities of poorly attractive traps may underperform expectations. Variable density designs demonstrated potential for cost savings but highlighted that resource-intensive outer bands are critical to boundary determination. Results suggesting that many grids are oversized need empirical verification, whereas other principles, such as using circular shapes, are readily adoptable now.

Structure-Guided In Vitro to In Vivo Pharmacokinetic Optimization of Propargyl-Linked Antifolates.

Pharmacokinetic/pharmacodynamic properties are strongly correlated with the in vivo efficacy of antibiotics. Propargyl-linked antifolates, a novel class of antibiotics, demonstrate potent antibacterial activity against both Gram-positive and Gram-negative pathogenic bacteria, including multidrug-resistant Staphylococcus aureus Here, we report our efforts to optimize the pharmacokinetic profile of this class to best match the established pharmacodynamic properties. High-resolution crystal structures were used in combination with in vitro pharmacokinetic models to design compounds that not only are metabolically stable in vivo but also retain potent antibacterial activity. The initial lead compound was prone to both N-oxidation and demethylation, which resulted in an abbreviated in vivo half-life (∼20 minutes) in mice. Stability of leads toward mouse liver microsomes was primarily used to guide medicinal chemistry efforts so robust efficacy could be demonstrated in a mouse disease model. Structure-based drug design guided mitigation of N-oxide formation through substitutions of sterically demanding groups adjacent to the pyridyl nitrogen. Additionally, deuterium and fluorine substitutions were evaluated for their effect on the rate of oxidative demethylation. The resulting compound was characterized and demonstrated to have a low projected clearance in humans with limited potential for drug-drug interactions as predicted by cytochrome P450 inhibition as well as an in vivo exposure profile that optimizes the potential for bactericidal activity, highlighting how structural data, merged with substitutions to introduce metabolic stability, are a powerful approach to drug design.

Quantitative Uncertainty Analysis for a Weed Risk Assessment System.

Weed risk assessments (WRA) are used to identify plant invaders before introduction. Unfortunately, very few incorporate uncertainty ratings or evaluate the effects of uncertainty, a fundamental risk component. We developed a probabilistic model to quantitatively evaluate the effects of uncertainty on the outcomes of a question-based WRA tool for the United States. In our tool, the uncertainty of each response is rated as Negligible, Low, Moderate, or High. We developed the model by specifying the likelihood of a response changing for each uncertainty rating. The simulations determine if responses change, select new responses, and sum the scores to determine the risk rating. The simulated scores reveal potential variation in WRA risk ratings. In testing with 204 species assessments, the ranges of simulated risk scores increased with greater uncertainty, and analyses for most species produced simulated risk ratings that differed from the baseline WRA rating. Still, the most frequent simulated rating matched the baseline rating for every High Risk species, and for 87% of all tested species. The remaining 13% primarily involved ambiguous Low Risk results. Changing final ratings based on the uncertainty analysis results was not justified here because accuracy (match between WRA tool and known risk rating) did not improve. Detailed analyses of three species assessments indicate that assessment uncertainty may be best reduced by obtaining evidence for unanswered questions, rather than obtaining additional evidence for questions with responses. This analysis represents an advance in interpreting WRA results, and has enhanced our regulation and management of potential weed species.

Relationships of abdominal pain, reports to visceral and temperature pain sensitivity, conditioned pain modulation, and heart rate variability in irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a heterogeneous condition with a number of pathophysiological mechanisms that appear to contribute to symptom chronicity. One of these is altered pain sensitivity. METHODS: Women between ages 18-45 were recruited the community. Of those enrolled, 56 had IBS and 36 were healthy control (HC) women. Participants completed questionnaires, kept a 4-week symptom diary and had a 12-h Holter placed to assess nighttime heart rate variability including high frequency power (HF), low frequency power (LF), and total power (TP). At mid-follicular phase approximately 80% of women completed a thermal pain sensitivity test with conditioned pain modulation and visceral pain sensitivity using a water load symptom provocation (WLSP) test. KEY RESULTS: As expected, daily abdominal pain was significantly higher in the IBS compared to HC group. There were no differences between the bowel pattern subgroups (IBS-diarrhea [IBS-D], IBS-constipation plus mixed [IBS-CM]). Thermal pain sensitivity did not differ between the IBS and the HC groups, but was significantly higher in the IBS-CM group than the IBS-D group. In the WLSP test, the IBS group experienced significantly more symptom distress than HCs and the IBS-CM group was higher than the IBS-D group. Heart rate variability indicators did not differ between the groups or IBS subgroups. Daily abdominal pain was positively correlated with LF and TP in the IBS group. CONCLUSIONS & INFERENCES: Despite similar levels of abdominal pain in IBS, the IBS-CM group demonstrated greater sensitivity to both thermal and visceral testing procedures.

Pathology of thyroid cancer: summary and update.

This brief presentation attempts to summarize the pathologic characteristics and the results of recent studies of the major thyroid malignancies. The clinical information now available, as well as advanced histologic and cytologic techniques, should provide a sound basis for diagnosis, management and further study of these neoplasms.

Adenomatous tumors of the middle ear and mastoid.

Three cases of middle ear and mastoid neoplasms are reported as "adenomatous tumors" since in their search of the literature the authors did not find any previously described lesions with a similar histologic appearance and benign biologic behavior. Microscopically, all three tumors are similarly composed of solid cords and nests of closely-packed small cells having an epithelial appearance. Two distinct cell types are present: cuboidal cells, arranged in a rudimentary gland-like pattern, and angular cells forming irregular nests with no distinct pattern. All three tumors developed in patients in their 20's, over a period of months with minimal symptoms; yet in all of the lesions the tympanic membrane was intact at the time of initial examination. None of the neoplasms was diagnosed preoperatively, and, once removed, all three tumors were pathologic enigmas and therapeutic problems in view of the initial and subsequent consultant pathologic opinions; nevertheless, total local excision with preservation of the tympanic membrane would appear to be safe treatment in these cases. The term "adenomatous tumor" is applied to these three neoplasms because: 1. a true glandular epithelial origin warranting the term adenoma or adenocarcinoma cannot be proven; and 2. the biologic behavior and prognosis is not necessarily reflected by the histologic appearance. A more specific term reflecting the origin and behavior of these tumors does not appear possible without the study of further cases.