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Accurate liquid water modelling is challenging. Here the authors use X-ray micro-computed tomography, deep learned super-resolution, multi-label segmentation, and direct multiphase simulation to simulate fuel cell and guide fuel cell design.

Landslide susceptibility mapping (LSM) characterizes landslide potential, which is essential for assessing landslide risk and developing mitigation strategies. Despite the significant progress in LSM research over the past two decades, several long-standing issues, such as uncertainties related to training samples and model selection, remain inadequately addressed in the literature. In this study, we employed a physically based susceptibility model, PISA-m, to generate four different non-landslide data scenarios and combine them with mapped landslides from Magoffin County, Kentucky, for model training. We utilized two Bayesian network model structures, Naïve Bayes (NB) and Tree-Augmented Naïve Bayes (TAN), to produce LSMs based on regional geomorphic conditions. After internal validation, we evaluated the robustness and reliability of the models using an independent landslide inventory from Owsley County, Kentucky. The results revealed considerable differences between the most effective model in internal validation (AUC = 0.969), which used non-landslide samples extracted exclusively from low susceptibility areas predicted by PISA-m, and the models’ unsatisfactory performance in external validation, as manifested by the identification of only 79.1% of landslide initiation points as high susceptibility areas. The obtained results from both internal and external validation highlighted the potential overfitting problem, which has largely been overlooked by previous studies. Additionally, our findings also indicate that TAN models consistently outperformed NB models when training datasets were the same due to the ability to account for variables’ dependencies by the former.

Rapidly changing remote sensing technologies (lidar, aerial photography, satellites) provide opportunities to improve regional-scale landslide risk mapping. However, data limitations regarding landslide hazard and exposure data influence how landslide risk is calculated. To develop risk assessments for a landslide-prone region of eastern Kentucky, USA, we assessed risk modeling and applicability using variable quality data. First, we used a risk equation that incorporated the hazard as a logistic regression landslide susceptibility model using geomorphic variables derived from lidar data. Susceptibility is calculated as a probability of occurrence. The exposure data included population, roads, railroads, and land class. Our vulnerability value was assumed to equal one (worst-case scenario for a degree of loss) and consequence data was economic cost. Results indicate 64.1 percent of the study area is classified as moderate to high socioeconomic risk. To develop a more data-limited approach, we used a 30 m slope-angle map as the hazard input and simplified exposure data. Results for the slope-based approach show the distribution of risk that is less uniform, with large areas of over-and under-prediction. Changes in the hazard and exposure inputs result in significant changes in the quality and applicability of the maps and demonstrate the broad range of risk modelling approaches.

Objectives: This retrospective, cross-sectional study investigated the nature and extent of burden experienced by caregivers of children and adolescents with chronic pain, and factors associated with increased caregiver burden., Methods: The Pediatric Electronic Persistent Pain Outcomes Collaboration database provided prospectively collected data from 1929 families attending 9 pediatric chronic pain services across Australia and New Zealand. Data included demographic information, responses to child pain and functioning measures, caregiver work impairment, and psychosocial functioning., Results: Caregivers of children with chronic pain reported work impairment associated with their child's pain (mean: 15% ± SD 25 absenteeism; 38% ± SD 29 productivity lost), significantly worse than published international population norms (large-scale community survey data), most other caregiver samples of adults and children with other chronic conditions, and adult samples with various pain conditions. Caregivers reported considerable burden in multiple psychosocial functioning domains, particularly leisure functioning, pain-related catastrophizing, and adverse parenting behaviors (with greater pain-related avoidance). Caregiver psychosocial burden was significantly associated with child psychosocial functioning (β = -0.308, P < 0.01), school absenteeism (β = 0.161, P < 0.01), physical disability (β = 0.096, P < 0.05), and pain duration (β = 0.084, P < 0.05), but not pain intensity. Caregiver work productivity loss was significantly associated with school absenteeism (β = 0.290, P < 0.01), child physical disability (β = 0.148, P < 0.01), child health care utilization (β = 0.118, P < 0.05), and worst pain intensity (β = 0.101, P < 0.05)., Discussion: These results highlight the significant and varied impacts experienced by caregivers of children with chronic pain. This work is novel in reporting significant work impairment and confirms psychosocial burden in a larger sample than previous studies., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

A proportion of youth with chronic pain do not respond to interdisciplinary pain management and may require transition to adult pain services. This study sought to characterize a cohort of patients referred to pediatric pain services who subsequently required referral to an adult pain service. We compared this transition group with pediatric patients eligible by age to transition but who did not transition to adult services. We sought to identify factors predicting the need to transition to adult pain services. This retrospective study utilized linkage data from the adult electronic Persistent Pain Outcomes Collaboration (ePPOC) and the pediatric (PaedePPOC) data repositories. The transition group experienced significantly higher pain intensity and disability, lower quality of life, and higher health care utilization relative to the comparison group. Parents of the transition group reported greater distress, catastrophizing, and helplessness relative to parents in the comparison group. Three factors significantly predicted transition: compensation status (OR = 4.21 (1.185-15)), daily anti-inflammatory medication use (OR = 2 (1.028-3.9)), and older age at referral (OR = 1.6 (1.3-2.17)). This study demonstrated that patients referred to pediatric pain services who subsequently need transition to adult services are a uniquely disabled and vulnerable group beyond comparative peers. Clinical applications for transition-specific care are discussed.

Background: Double balloon enteroscopy remains a resource and time-intensive procedure that is not available in many endoscopy units., Aims: We aimed to identify variables impacting the speed and completion of double balloon enteroscopy., Methods: We retrospectively reviewed 550 patients. Using a mean time and distance for both the antegrade and retrograde approach, we determined the procedure speed and assessed factors that influenced it. In addition, we assessed the factors that contributed to a complete double balloon enteroscopy., Results: A total of 386 antegrade and 164 retrograde double balloon enteroscopies were performed. Greater than 10 AVMs requiring treatment was a negative predictor (AOR 0.25, CI 0.11-0.51, p < 0.001), whereas age greater than 60 years (AOR 2.66, CI 1.18-6.65, p = 0.025) was a positive predictor of a fast antegrade enteroscopy. For retrograde, prior abdominal surgery was the only factor that trended to significance (AOR 0.38, CI 0.14-0.99, p = 0.052). A total of 120 combined procedures were performed. Female gender (AOR 2.62, CI 1.16-6.24, p = 0.02), history of prior abdominal surgery (AOR 0.31, CI 0.13-0.70, p = 0.006) and Boston bowel pre-preparation score of greater than 6 (AOR 4.50, CI 1.59-14.30, p = 0.006) were the only significant predictors of a complete procedure., Conclusion: By applying double balloon enteroscopy speed, a novel method of measuring procedure efficiency, we were able to more reliably identify the factors that will negatively impact the speed and success of the procedure., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Relatively little is known about the influence of extreme body weight on the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of drugs used in many disease states. While direct oral anticoagulants (DOACs) have an advantage over warfarin in that they do not require routine drug monitoring, some may regard this convenience as less compelling in obese patients. Some consensus guidelines discourage using DOACs in patients weighing > 120 kg or with a body mass index > 35-40 kg/m 2 , given a sparsity of available data in this population and the concern that fixed dosing in obese patients might lead to decreased drug exposure and lower efficacy. Per the prescribing information, apixaban does not require dose adjustment in patients weighing above a certain threshold (e.g., ≥ 120 kg). Data from healthy volunteers and patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) have shown that increased body weight has a modest effect on apixaban's PK. However, the paucity of exposure data in individuals > 120 kg and the lack of guideline consensus on DOAC use in obese patients continue to raise concerns about potential decreased drug exposure at extreme weight. This article is the first to comprehensively review the available PK data in obese individuals without NVAF or VTE, and PK, PD, efficacy, effectiveness, and safety data for apixaban in obese patients with either NVAF or VTE, including subgroup analyses across randomized controlled trials and observational (real-world) studies. These data suggest that obesity does not substantially influence the efficacy, effectiveness, or safety of apixaban in these patients. Trial Registration ARISTOTLE: NCT00412984; AVERROES: NCT00496769; AMPLIFY: NCT00643201; AMPLIFY-EXT: NCT00633893; ADVANCE-1: NCT00371683; ADVANCE-2: NCT00452530; ADVANCE-3: NCT00423319 Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data (MP4 161.22 MB)., (© 2022. © Pfizer.)

Background: Pulmonary nodules in elderly patients are commonly encountered in clinical practice. Tissue sampling with image guided transthoracic needle aspiration is often performed but may be complicated by pneumothorax or bleeding. To understand the outcomes of transthoracic needle aspiration in the elderly, we retrospectively reviewed outcomes of patients age 75 or greater in a single tertiary center., Methods: Four-hundred eleven patients age 75 or greater with a pulmonary nodule identified on computed tomography who underwent needle aspiration of the lung were studied. Diagnostic yield and procedural complications were assessed for each patient and subgroups analysis of those age 85 or greater was performed., Results: Malignancy was confirmed in 70% of subjects and a benign diagnosis identified in 9%. Of the 411 patents, 203 (49.4%) experienced a complication; 150 patients (36.5%) developed a pneumothorax and 79 (19.2%) had bleeding. No patient required transfusion, experienced persistent air leak or massive hemoptysis, air embolism or death. Post procedural hospitalization was required in 36 patients (8.8%) with a median hospital stay of 2 days. No factors were identified to be associated with occurrence of a complication (all p ≥ 0.16) and complications were not increased in those 85 or greater., Conclusion: Our results suggest that in an elderly population, image guided needle aspiration of a pulmonary nodule provides diagnostic findings in most patients. Procedural complications following are not uncommon but the severity and long-term impact are limited. The occurrence of complications is similar in those age 75-84 and age 85 and older.

Study Design: Cohort analysis., Objective: Document satisfaction with management and appearance concerns in children of different ethnicity who underwent spinal fusion/instrumentation for adolescent idiopathic scoliosis (AIS)., Summary of Background Data: Scoliosis Research Society Questionnaire (SRS-30) outcomes in AIS indicate a link between appearance and satisfaction as well as ethnic variation in appearance domain. Exploration of these findings in the Scoliosis Appearance Questionnaire (SAQ) will allow better understanding of ethnic variation in appearance concerns., Methods: Children with AIS who underwent posterior-only operations and completed the SAQ's question 31 were identified. Univariate logistic regression of SAQ questions 12-30 was used to assess relationships with ethnicity., Results: 1,977 children [boys: 281, girls: 1,290, unspecified: 406; average age 15.1 ± 2.0 years preoperatively and 817 children (boys: 113, girls: 569, unspecified: 135; average age 15.1 ± 2.0 years) at 2 years' follow-up met inclusion criteria. The majority were Caucasian (57.3%). Few were Hispanic (3.4%). Preoperatively, the largest percentage of patients in each ethnic group answered "very true" to "wanting to be more even." Preoperatively, Asians were least likely to be concerned about evenness of shoulders, hips, waist, ribs, and chest in back (p < .05); however, they expressed greatest concern about height (p < .05). African Americans and Hispanics were more likely to be concerned about breast evenness and anterior chest and looking better in clothes (p < .05). African Americans were most concerned about overall evenness and evenness of shoulders, hips, waist, ribs, posterior chest, leg length, and looking more attractive (p < .05). Surgical scar was most important postoperatively for all ethnicities. African Americans and Hispanics were more self-conscious about scar (p < .05). African Americans were most likely to want to be more even and have more even shoulders, hips, waist, leg lengths, ribs, breasts, and chest postoperatively., Conclusions: Ethnicity influenced appearance concerns in pre- and postoperative SAQ evaluation. Ethnic variation in appearance concerns should be taken into account and differentiated when counseling patients about AIS and surgical correction., Level of Evidence: Level III., (Copyright © 2017 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Diabetes is a metabolic disease characterized by elevated levels of plasma glucose. When untreated, diabetes increases the risk of developing co-morbidities such as cardiovascular disease. Several drugs, often used as part of combination therapies, have been approved to treat the disease, but these drugs will eventually fail to effectively control blood glucose levels, at which point insulin replacement therapy is required. A medical need exists for new antidiabetic drugs that exhibit good efficacy with improved safety/toleration profiles and can be added on top of existing therapies, or that can provide additional benefits beyond glucose lowering such as pancreatic beta (β)-cell protection., Areas Covered: This review analyzes drug targets and applicants of patents that published between 2011-2016 claiming novel small or large molecules for the treatment of diabetes, and compares the results to the 2008-2010 time period., Expert Opinion: A majority of patent activity around the discovery of new antidiabetic drugs in 2011-2016 was directed against 15 targets, most of which were also the focus of drug discovery efforts in the 2008-2010 time period. The top targets by total patent counts were DPP4, GLP1R, INSR, GPR119, and SGLT2 (SLC5A2). With the exception of GPR119, these are the pharmacological targets of some of the best-selling antidiabetic drugs currently on the market. The top targets of patent families with the largest size counts, a metric useful in assessing patent value and applicant interest, were AMPK, CALCR, DPP4, and GLP1R. The patent analysis identified several emerging targets with greater patent activity in 2011-2016 compared to 2008-2010, including FFAR1, FFAR4, and FGFR1. Most of the patent activity in 2011-2016 was directed at established and precedented diabetes targets, the modulation of which may lead to improvements in glucose control and a delay in the progression of the disease. Few targets were identified that promote pancreatic β-cell regeneration and β-cell health, areas where future opportunities may exist for developing transformative drug therapies that may potentially lead to cures for diabetes.

Background: Common childhood pain conditions (nonmigraine headache, migraine, recurrent abdominal pain, growing pains, low back pain) and persistent pains are often associated with each other and have significant implications in later life. Emerging evidence suggests additional associations between these pain conditions and restless legs syndrome, iron deficiency, anxiety, and depression. The aim of this cross-sectional study in pediatric twin individuals and their siblings was to investigate these associations., Materials and Methods: Surveys were sent to Australian twin families via the Australian Twin Registry, yielding responses from 2530 pediatric individuals. The lifetime prevalence of the common pain disorders of childhood and of other persistent pains, restless legs syndrome and iron deficiency, and anxious/depressed score were determined by questionnaires. Random-effects logistic regression modeling was used to investigate univariate and multivariate associations between conditions., Results: Univariate associations were found between each of the pain conditions and persistent pain, and between the pain conditions with restless legs syndrome, iron deficiency, and anxious/depressed score. Derivative multivariate analyses retained statistically significant associations between each of the pain disorders included in the respective models (odds ratios [OR], 1.69-7.04) with the exception of growing pains with persistent pain. Of the nonpain conditions included in the multivariate analyses, restless legs syndrome remained associated with growing pains (OR, 8.50) and persistent pain (OR, 2.01). Iron deficiency remained significantly associated with migraine (OR, 2.38), persistent pain (OR, 3.70), and restless legs syndrome (OR, 5.10)., Conclusions: In light of their extensive associations, the common pain conditions, persistent pain, restless legs syndrome, iron deficiency, anxiety and depression, are likely to involve common etiological mechanisms that warrant further investigation.

Background: To evaluate the accuracy and precision of a method for serum aldosterone using supported liquid extraction (SLE) for sample preparation instead of the more conventional liquid-liquid extraction (LLE) approach., Methods: Two independently developed SLE-based LC-MS/MS methods for serum aldosterone (sample volumes 250 μl and 300 μl respectively) were compared to a modification of a previously reported LLE approach (sample volume 500 μl) in two method comparisons (n=75 and n=97). SLE analyses were performed at two separate centres. Precision was evaluated at a single site using human pools in head-to-head comparison between SLE and LLE. All analyses were performed on the ABSCIEX API-5000 LC-MS/MS system., Results: At four increasing pool concentrations spanning 67-1060 pmol/l, total precision for SLE ranged from 6.8-4.1% compared with 11.1-4.3% for LLE. Differences did not reach statistical significance except at the lowest concentration where SLE was superior. Pasing Bablok regression comparisons were SLE=0.96×LLE-5.8 pmol/l (R(2)=0.985) and SLE=0.96×LLE-0.44 pmol/l (R(2)=0.969)., Conclusions: For analysis of serum aldosterone on the ABSCIEX API-5000, SLE affords a smaller sample volume while maintaining the accuracy and precision performance of LLE. By avoiding specimen vortexing, SLE also allows for greater automation in the sample preparation.

Joint position sense is believed to be mediated by muscle afferent signals. Because a "phantom" hand produced by a sensory and motor nerve block appears to move in the direction of voluntary effort, signals of "motor command" or "effort" can influence perceived joint position. To determine whether this occurs when sensory signals are available, three studies assessed position sense when motor command and afferent signals were available, but joint movement was prevented. First, the hand was positioned to stop movement at the proximal joint of the middle finger, and movement at the distal joint was impossible because the muscles had been "disengaged". Voluntary efforts produced illusory position changes in the direction of the effort (12.6 +/- 2.0 degrees distal joint; 12.3 +/- 2.3 degrees proximal joint for efforts at 30% maximum; means +/- SD). Second, when subjects attempted to move the index finger under isometric conditions, the index finger appeared to move 7.4 +/- 1.2 degrees in the direction of efforts. These illusions graded with the level of effort (10 or 30% maximum) and far exceeded any real joint movement. Finally, because changes in muscle afferent feedback might have accompanied the voluntary efforts, all forearm and hand muscles were completely paralyzed by locally infused rocuronium. During paralysis, passive wrist position was signaled accurately, but, during attempted efforts (30% maximum), perceived wrist position changed by 9.7 +/- 4.9 degrees . Before paralysis, isometric efforts changed it by 6.7 +/- 3.6 degrees . Thus all studies concur: when joint movement is prevented, signals of motor command contribute to joint position sense.

A consortium of investigators is engaged in a functional genomics project centered on the filamentous fungus Neurospora, with an eye to opening up the functional genomic analysis of all the filamentous fungi. The overall goal of the four interdependent projects in this effort is to accomplish functional genomics, annotation, and expression analyses of Neurospora crassa, a filamentous fungus that is an established model for the assemblage of over 250,000 species of non yeast fungi. Building from the completely sequenced 43-Mb Neurospora genome, Project 1 is pursuing the systematic disruption of genes through targeted gene replacements, phenotypic analysis of mutant strains, and their distribution to the scientific community at large. Project 2, through a primary focus in Annotation and Bioinformatics, has developed a platform for electronically capturing community feedback and data about the existing annotation, while building and maintaining a database to capture and display information about phenotypes. Oligonucleotide-based microarrays created in Project 3 are being used to collect baseline expression data for the nearly 11,000 distinguishable transcripts in Neurospora under various conditions of growth and development, and eventually to begin to analyze the global effects of loss of novel genes in strains created by Project 1. cDNA libraries generated in Project 4 document the overall complexity of expressed sequences in Neurospora, including alternative splicing alternative promoters and antisense transcripts. In addition, these studies have driven the assembly of an SNP map presently populated by nearly 300 markers that will greatly accelerate the positional cloning of genes.

The role of afferent inflow and efferent outflow (or command) signals in judgements of limb position has been debated for over a century. One way to assess this is to check for changes during complete paralysis, with the current view being that perceived movements or position changes do not usually accompany attempts to contract paralysed muscles. To re-examine this, we asked six naïve subjects to carry out a simple position-matching task at the wrist. In the absence of vision, subjects accurately perceived the position to which their right wrist had been moved by the experimenter by matching it with their left hand. There was no significant change in perception when position was matched during sustained flexion or extension efforts. Then we paralysed and anaesthetized the right arm with ischaemia in order to produce a 'phantom' hand. The perceived position of the wrist changed by more than 20 deg when subjects attempted to flex or extend their hand when it was paralysed and anaesthetized. Further studies showed that this illusion was not dependent on the way in which the paralysis was produced and that the size of the position illusion increased when the level of effort during paralysis increased. These results establish for the first time a definitive role for 'outflow' signals in position sense.

Background: Numerous studies have investigated patient outcomes of cardiac surgery, including some examining health-related quality of life. While these studies have provided some insight into patients' physical function, social abilities and perceived quality of life, studies examining the experiences of individuals recovering from cardiac surgery have received only limited investigation., Aims: This paper presents a thematic analysis of interviews conducted with patients recovering from cardiothoracic surgery, about their memories and experiences of hospital and recovery post-hospital discharge., Methods: Using an exploratory qualitative approach, eight participants were interviewed 6 months following their surgery. Transcripts of interviews were examined using a content analysis approach, with open coding of text and categorising of similar concepts into themes., Findings: Participants reported varying degrees of pain and physical dysfunction during their recovery from surgery and some had still not returned to optimal function. Seven themes emerged from the data: impressions of ICU; comfort/discomfort; being sick/getting better; companionship/isolation; hope/hopelessness; acceptance/apprehension; and life changes. A number of the themes were constructed as a continuum, with participants often demonstrating a range of views or experiences. Many had little or no memory of their stay in the intensive care unit, although others had vivid recollections. Their impressions of hospital were mostly positive, although many experienced fear, apprehension, and mood disturbances at some time during their recovery. Most participants recalled being sick, reaching a turning point, and then getting better. Many participants reported a change in life view since their recovery from surgery., Conclusions: Attention to specific areas of patient orientation, education and support was identified to facilitate realistic expectations of recovery. In addition, some form of systematic follow-up that focuses on patient recovery in terms of both physical and psychological function is important.

Recovery from a critical illness can be a complex and protracted process. It is known that for some, health-related quality of life (HRQOL) does not return to pre-illness levels for many months, and in some disease processes this may be longer. This study was undertaken as part of a larger project examining the pain and health status of survivors of a critical illness. The aims of the qualitative aspect of the study were to examine the participants' memories of intensive care and hospitalisation at 6 months post-discharge, and to explore the impact of the critical illness experience on their recovery. Purposive sampling was used to enable rich descriptions of the experience of recovery from those patients best able to articulate their experiences. Three common themes were found with our six participants: recollections, responses, and comfort/discomfort. Recovery from their critical illness continued to affect the participants and carers, some profoundly so. Better integration of services and continued support is required for survivors of a critical illness up to and beyond 6 months.

Intensive care unit (ICU) survivors report reductions in health-related quality of life (HR-QOL), whilst chronic pain is common in the general population. However, it is unknown whether there are associations between the experience of ICU and the incidence of chronic pain. A questionnaire--Pain Scale, Pain Self-Efficacy Questionnaire (PSEQ), Centre of Epidemiology Study Depression Scale (CES-D Scale) and the Short Form Health Survey (SF-36)--was sent to 99 consenting patients who had been in the ICU for >48 hours. Sixty-six and 52 questionnaires were returned at 1 and 6 months respectively. There was a general limitation in activities of daily living; younger ages (36-65 years) experienced a decease in work performance and other physical activities. Bodily pain increased, general health diminished, and engagements in social activities were severely affected. There was a decline in mental health for those 36-65 years of age. HR-QOL improved over time; 28% experienced chronic pain and had longer hospital length of stay (LOS), tended to have longer ICU LOS and were ventilated for longer. Those with chronic pain had significant reductions in physical function, bodily pain, general health and vitality. Ventilator hours and hospital LOS were associated with risk of chronic pain (OR 1.09, p=0.033 and OR 1.27, p=0.046). HR-QOL in ICU survivors declined, although there was a general improvement from 1-6 months. This decline in HR-QOL affected younger people (less than 65 years) more than older people. Chronic pain is a significant issue post ICU and is associated with poorer HR-QOL.

We aligned Incyte ESTs and publicly available sequences to the rat genome and analyzed rat chromosome 1q43-54, a region in which several quantitative trait loci (QTLs) have been identified, including renal disease, diabetes, hypertension, body weight, and encephalomyelitis. Within this region, which contains 255 Ensembl gene predictions, the aligned sequences clustered into 568 Incyte genes and gene fragments. Of the Incyte genes, 261 (46%) overlapped 184 (72%) of the Ensembl gene predictions, whereas 307 were unique to Incyte. The rat-to-human syntenic map displays rearrangement of this region on rat chr. 1 onto human chromosomes 9 and 10. The mapping of corresponding human disease phenotypes to either one of these chromosomes has allowed us to focus in on genes associated with disease phenotypes. As an example, we have used the syntenic information for the rat Rf-1 disease region and the orthologous human ESRD disease region to reduce the size of the original rat QTL to only 11.5 Mb. Using the syntenic information in combination with expression data from ESTs and microarrays, we have selected a set of 66 candidate disease genes for Rf-1. The combination of the results from these different analyses represents a powerful approach for narrowing the number of genes that could play a role in the development of complex diseases.

Plant hybrids can be more, less, or equally resistant to herbivores compared to their parental species. These patterns in resistance can be critical determinants of the fitness of plant hybrids and may also influence distribution of the herbivore. We examined resistance to a pre-dispersal seed predator by natural and experimental hybrids between Ipomopsis aggregata and I. tenuituba. These species and their hybrid offspring differed primarily in ability to avoid oviposition by Hylemya sp. (Diptera: Anthomyiidae) rather than in reducing damage to seeds by a developing larva. Plants of I. tenuituba had the lowest frequency of fly eggs and were thus the most successful at avoiding damage. Hybrids were either intermediate to or less resistant than both parental species. Because these patterns persisted in experimental arrays of interspersed potted plants, they cannot be attributed to ongoing differences in the environment between hybrid and parental sites. In experimental arrays, the frequency of fly eggs correlated positively with corolla width, a dimension of flower size that also influences the rate of pollination, suggesting seed predators can generate selection on reproductive traits of hybrids. Furthermore, in one of the arrays, oviposition on F2 hybrids exceeded the average for the F1 and the midparent. Our results underscore the need to consider genetic background of hybrids in assessing plant responses to herbivores.