Washington Research Foundation

SynopsisInsects have a keen ability to detect numerous odors in their environment. These odors, known as volatile organic compounds (VOCs), provide the insect with information about food, predators, and mates that may be in the area and are detected by olfactory receptors expressed by sensory neurons on the antennae. When VOCs are transduced by the olfactory sensory neurons, the antennal electrical potential dynamically changes, causing a local field potential (LFP) response to occur. Research has used the LFP amplitude for determining VOC concentration, but only recently have antennal LFPs been posited to be able to be used for VOC discrimination and identification. To close this gap, we use the time-series response of the antenna to odors as well as principal components of these responses to capture the characteristics of the LFP response, including waveform dynamics, intensity, slope, and duration. We use antennae of the Manduca sexta moth to record LFPs generated in response to Floral and disease associated VOC’s. Using machine learning approaches (support vector machines and random forests) trained on the LFP responses, we were able to predict and classify individual VOCs across a range of concentrations, as well as complex mixtures that elicited a given LFP waveform from an excised antenna. These results demonstrate that antennal olfactory responses can be used for the classification of differing VOC features, including concentration, identity, and duration, and have implications for diverse chemical sensing applications, such as search-and-rescue, the presence of agricultural pests, and the presence of human disease.

Chewing herbivores activate plant defense responses through a combination of mechanical wounding and elicitation by herbivore-associated molecular patterns (HAMPs). HAMPs are wound response amplifiers; however, specific defense outputs may also exist that strictly require HAMP-mediated defense signaling. To investigate HAMP-mediated signaling and defense responses, we characterized cowpea (Vigna unguiculata) transcriptome changes following elicitation by inceptin, a peptide HAMP common in Lepidoptera larvae oral secretions. Following inceptin treatment, we observed large-scale reprogramming of the transcriptome consistent with three different response categories: (i) amplification of mechanical wound responses, (ii) temporal extension through accelerated or prolonged responses, and (iii) examples of inceptin-specific elicitation and suppression. At both early and late timepoints, namely 1 and 6 h, large sets of transcripts specifically accumulated following inceptin elicitation. Further early inceptin-regulated transcripts were classified as reversing changes induced by wounding alone. Within key signaling- and defense-related gene families, inceptin-elicited responses included target subsets of wound-induced transcripts. Transcripts displaying the largest inceptin-elicited fold changes included transcripts encoding terpene synthases (TPSs) and peroxidases (POXs) that correspond with induced volatile production and increased POX activity in cowpea. Characterization of inceptin-elicited cowpea defenses via heterologous expression in Nicotiana benthamiana demonstrated that specific cowpea TPSs and POXs were able to confer terpene emission and the reduced growth of beet armyworm (Spodoptera exigua) herbivores, respectively. Collectively, our present findings in cowpea support a model where HAMP elicitation both amplifies concurrent wound responses and specifically contributes to the activation of selective outputs associated with direct and indirect antiherbivore defenses.

Publication bias has the potential to adversely impact clinical decision making and patient health if alternative decisions would have been made had there been complete publication of evidence. The objective of our analysis was to determine if earlier publication of the complete evidence on rosiglitazone's risk of myocardial infarction (MI) would have changed clinical decision making at an earlier point in time. We tested several methods for adjustment of publication bias to assess the impact of potential time delays to identifying the MI effect. We then performed a cumulative meta-analysis (CMA) for both published studies (published-only data set) and all studies performed (comprehensive data set). We then created an adjusted data set using existing methods of adjustment for publication bias (Harbord regression, Peter's regression, and the nonparametric trim and fill method) applied to the limited data set. Finally, we compared the time to the decision threshold for each data set using CMA. Although published-only and comprehensive data sets did not provide notably different final summary estimates [OR=1.4 (95 percent confidence interval [CI]: .95-2.05) and 1.42 (95 percent CI: 1.03-1.97)], the comprehensive data set reached the decision threshold 36months earlier than the published-only data set. All three adjustment methods tested did not show a differential time to decision threshold versus the published-only data set. Complete access to studies capturing MI risk for rosiglitazone would have led to the evidence reaching a clinically meaningful decision threshold 3years earlier.

Type 1 diabetes (T1D) TrialNet is a National Institutes of Health-sponsored clinical trial network aimed at altering the disease course of T1D. The purpose of this study is to evaluate age-dependent heterogeneity in clinical, metabolic and immunologic characteristics of individuals with recent-onset T1D, to identify cohorts of interest and to aid in planning of future studies. Eight hundred eighty-three individuals with recent-onset T1D involved in five TrialNet studies were categorized by age as follows: ≥18 years, 12-17 years, 8-12 years and <8 years. Data were compared with healthy age-matched subjects in the National Health and Nutrition Examination Survey. Only 2.0% of the individuals overall were excluded from trial participation because of insufficient C-peptide values (<0.2 pmol/mL). A disproportionate number of these subjects were <8 years old. Leukopenia was present in 21.2% of individuals and lymphopenia in 11.6%; these frequencies were markedly higher than age-matched healthy National Health and Nutrition Examination Survey population. Of the cohort, 24.5% were overweight or obese. Neither high-risk human leukocyte antigen type DR3 nor DR4 was present in 31% of adults and 21% of children. The ability of recent-onset T1D patients to meet key entry criteria for TrialNet studies, including C-peptide >0.2 pmol/mL, varies by age. Lower C-peptide level requirements for younger participants and other aspects of heterogeneity of recent-onset T1D patients, such as white blood cell count abnormalities and body mass index should be considered in the design of future clinical studies.

The current study follows a sample of lower skilled language minority (LM) and native English-speaking (non-LM) students who participated in an efficacy trial of a kindergarten phonics-based intervention. Follow-up procedures allowed 93% of the original sample to be retained for simple treatment effects modeling (N = 78 LM and N = 59 non-LM) and 72% to be retained for classroom instruction modeling (N = 62 LM and N = 44 non-LM). Simple treatment effects on longer term outcomes were detected on word reading, spelling, and comprehension outcomes for LM students (approximate effect sizes averaged 0.27); comparatively, treatment effects for non-LM students were detected on all outcomes, including fluency (approximate effect sizes averaged 0.54). Instructional model results showed that greater time in Grade 1 word study instruction and Grade 2 meaning instruction was associated with higher reading scores for LM students at the end of second grade, irrespective of experimental condition. For non-LM children, greater time in Grade 1 meaning instruction was connected with higher reading scores at the end of Grade 2, irrespective of experimental condition. Finally, kindergarten intervention effects tended to be greater for both LM and non-LM students who received more Grade 1 word study instruction and more Grade 2 meaning instruction. Limitations and practical implications are discussed.

This study examined teachers' receptivity to, and the factors that influence their use of, a practice new to classroom teachers for including students with learning disabilities, classwide peer tutoring (cwpt; fuchs, mathes,' fuchs, 1993). Cwpt is a whole-class approach that uses teacher-orchestrated procedures and peer-mediated practice to supplement reading instruction. forty-four teachers in eight elementary schools participated; 29 teachers in a high-support group received honoraria and access to release time and technical assistance in order to learn about cwpt and how to implement it; 15 teachers in a low-support group received only a copy of the cwpt manual. all teachers attended a 40-minute presentation on cwpt that provided an overview on its components and benefits. measures included surveys administered before and after the initial presentations, observations midpoint in teachers' implementation of cwpt, interim interviews and logs, and a follow-up interview and observation of a subgroup of four imple-mentors. the survey responses of 44 teachers were analyzed and the six implementors were observed and interviewed. results indicated that level of support did not significantly influence teacher interest in or use of cwpt. all implementors made some modifications in the cwpt procedures. discussion focuses on factors that might have influenced teacher Interest in cwpt, their implementation rates, and reasons for teachers' modifications of the practice.