Clinical efficacy and implementation issues of an electronic pain reporting device among outpatients with cancer.

PURPOSE: Collecting patients' pain features for congruent pain relief treatment is time-consuming. We sought to identify implementation issues and evaluate the efficacy of an electronic patient self-reporting pain device in community-based cancer clinics. METHODS: In a 2-phase descriptive pilot and randomized controlled trial (RCT) with pretest/posttest design, 178 cancer patients participated (n = 33 pilot phase; n = 145 in the RCT phase). Patients completed PAINReportIt®, an electronic version of the valid and reliable McGill Pain Questionnaire that comprehensively measures the multiple dimensions of pain. All pilot phase and RCT patients were asked to complete PAINReportIt® twice and received usual care. For RCT patients assigned to the experimental group, a copy of the PAINReportIt® Summary was placed in their clinic medical record before they visited their clinicians. Posttest measures were completed 3-7 days later. RESULTS: We identified three implementation barriers: system resistance to deposit of research data into the medical record, staff resistance to change, and patients' physical manipulation of the tablet. The time required to complete the tool did not differ significantly between groups but reduced significantly pre- to posttest in both RCT groups. Current pain intensity and pain quality but not worst pain scores decreased significantly pre- to posttest in the experimental group. None of the pain variables differed significantly between groups. CONCLUSION: Implementation of PAINReportIt® was feasible in community oncology clinic settings. Barriers identified were expected and were surmountable. The studied tool showed satisfactory time sparing for comprehensive pain assessment with data automatically recorded and easily accessed by the clinician in the form of a summary report. Findings support the need for additional research to demonstrate the clinical efficacy of tablet-based pain assessment on patient outcomes as well as clinical care processes such as pain documentation and analgesic prescriptions.

Eating quality of the longissimus thoracis muscle in beef cattle - Contributing factors to the underlying variability and associations with performance traits.

The objective was to determine the factors associated with meat tenderness, juiciness, flavour and chewiness in 4791 growing crossbred cattle. Meat quality of bulls was inferior to that of both steers and heifers with little difference between the latter two genders. Angus, Hereford and Belgian Blues had the most tender meat with the Simmental being the toughest albeit the difference was, on average, only 5%. Moderate to strong correlations (r ≥ |0.43|) existed among tenderness, juiciness and flavour although some of the correlations differed by animal gender. Correlations between chewiness and tenderness in the different genders varied from -0.81 to -0.74 while the correlations between chewiness and the other sensory traits varied from -0.54 to -0.09. The (partial) correlations between each of the four sensory metrics and all of carcass weight, carcass conformation and carcass fat score were ≤|0.09| with most not being different from zero. Correlations between the sensory traits with growth rate, muscle depth, feed intake and efficiency were all ≤|0.08| and mostly not different from zero.

Inter-animal genetic variability exist in organoleptic properties of prime beef meat.

The objective of the present study was to estimate genetic parameters for four organoleptic traits in beef meat, namely tenderness, juiciness, flavour and chewiness using data from 5380 young crossbred progeny of 748 different sires. As well as using the mean animal sensory score across all panellists for a given trait, other aggregate functions such as the median and modal values were also investigated. The heritability (SE) of mean tenderness, juiciness, flavour and chewiness was 0.16 (0.04), 0.14 (0.04), 0.11 (0.03) and 0.21 (0.06), respectively; heritability estimates for the other aggregate values of these traits were generally lower. All genetic correlations between tenderness, juiciness and flavour were positive (0.52 to 0.68) while the genetic correlations between these three traits with chewiness were all negative varying from -0.95 to -0.48. Weak genetic correlations (≤|0.16|) were evident between the sensory traits and all of carcass weight, conformation and subcutaneous fat cover.

Population structure and breed composition prediction in a multi-breed sheep population using genome-wide single nucleotide polymorphism genotypes.

Knowledge of population structure and breed composition of a population can be advantageous for a number of reasons; these include designing optimal (cross)breeding strategies in order to maximise non-additive genetic effects, maintaining flockbook integrity by authenticating animals being registered and as a quality control measure in the genotyping process. The objectives of the present study were to 1) describe the population structure of 24 sheep breeds, 2) quantify the breed composition of both flockbook-recorded and crossbred animals using single nucleotide polymorphism BLUP (SNP-BLUP), and 3) quantify the accuracy of breed composition prediction from low-density genotype panels containing between 2000 and 6000 SNPs. In total, 9334 autosomal SNPs on 11 144 flockbook-recorded animals and 1172 crossbred animals were used. The population structure of all breeds was characterised by principal component analysis (PCA) as well as the pairwise breed fixation index (Fst). The total number of animals, all of which were purebred, included in the calibration population for SNP-BLUP was 2579 with the number of animals per breed ranging from 9 to 500. The remaining 9559 flockbook-recorded animals, composite breeds and crossbred animals represented the test population; three breeds were excluded from breed composition prediction. The breed composition predicted using SNP-BLUP with 9334 SNPs was considered the gold standard prediction. The pairwise breed Fst ranged from 0.040 (between the Irish Blackface and Scottish Blackface) to 0.282 (between the Border Leicester and Suffolk). Principal component analysis revealed that the Suffolk from Ireland and the Suffolk from New Zealand formed distinct, non-overlapping clusters. In contrast, the Texel from Ireland and that from New Zealand formed integrated, overlapping clusters. Composite animals such as the Belclare clustered close to its founder breeds (i.e., Finn, Galway, Lleyn and Texel). When all 9334 SNPs were used to predict breed composition, an animal that had a majority breed proportion predicted to be ≥0.90 was defined as purebred for the present study. As the panel density decreased, the predicted breed proportion threshold, used to identify animals as purebred, also decreased (≥0.85 with 6000 SNPs to ≥0.60 with 2000 SNPs). In all, results from the study suggest that breed composition for purebred and crossbred animals can be determined with SNP-BLUP using ≥5000 SNPs.

Carcass characteristics of cattle differing in Jersey proportion.

Comparison of alternative dairy (cross-)breeding programs requires full appraisals of all revenues and costs, including beef merit. Few studies exist on carcass characteristics of crossbred dairy progeny originating from dairy herds as well as their dams. The objective of the present study was to quantify, using a national database, the carcass characteristics of young animals and cows differing in their fraction of Jersey. The data set consisted of 117,593 young animals and 42,799 cows. The associations between a combination of sire and dam breed proportion (just animal breed proportion when the dependent variable was on cows) with age at slaughter (just for young animals), carcass weight, conformation, fat score, price per kilogram, and total carcass value were estimated using mixed models that accounted for covariances among herdmates of the same sex slaughtered in close proximity in time; we also accounted for age at slaughter in young animals (which was substituted with carcass weight and carcass fat score when the dependent variable was age at slaughter), animal sex, parity of the cow or dam (where relevant), and temporal effects represented by a year-by-month 2-way interaction. For young animals, the heaviest of the dairy carcasses were from the mating of a Holstein-Friesian dam and a Holstein-Friesian sire (323.34 kg), whereas the lightest carcasses were from the mating of a purebred Jersey dam to a purebred Jersey sire which were 46.31 kg lighter (standard error of the difference = 1.21 kg). The young animal carcass weight of an F1 Holstein-Friesian × Jersey cross was 20.4 to 27.0 kg less than that of a purebred Holstein-Friesian animal. The carcass conformation of a Holstein-Friesian young animal was 26% superior to that of a purebred Jersey, translating to a difference of 0.78 conformation units on a scale of 1 to 15. Purebred Holstein-Friesians produced carcasses with less fat than their purebred Jersey counterparts. The difference in carcass price per kilogram among the alternative sire-dam breed combinations investigated was minimal, although large differences existed among the different breed types for overall carcass value; the carcass value of a Holstein-Friesian animal was 20% greater than that of a Jersey animal. Purebred Jersey animals required, on average, 21 d longer to reach a given carcass weight and fat score relative to a purebred Holstein-Friesian. The difference in age at slaughter between a purebred Holstein-Friesian animal and the mating between a Holstein-Friesian sire with a Jersey dam, and vice versa, was between 7.0 and 8.9 d. A 75.8-kg difference in carcass weight existed between the carcass of a purebred Jersey cow and that of a Holstein-Friesian cow; a 50% Holstein-Friesian-50% Jersey cow had a carcass 42.0 kg lighter than that of a purebred Holstein-Friesian cow. Carcass conformation was superior in purebred Holstein-Friesian compared with purebred Jersey cows. Results from this study represent useful input parameters to populate simulation models of alternative breeding programs on dairy farms, and to help beef farmers evaluate the cost-benefit of rearing, for slaughter, animals differing in Jersey fraction.

Heritability estimates of meat sensory characteristics are a function of the number of panellists and their inter-correlations.

The objective of the present study was to quantify, using simulated data, the impact on estimated heritability of varying the number of panellists and their inter-correlations using meat sensory tenderness in cattle as an example. Estimated parameters from actual sensory-based tenderness scores from 9 individual panellists on 1252 beef cattle were used to parameterise the simulation. A single "tenderness score" for each of 10 panellists was simulated for 15,000 cattle. Heritability estimates were calculated for each of the 10 panellists individually as well as the mean score per animal for all n combinations of panellists. Heritability estimates improved with increasing number of panellists in line with expectations from a deterministic equation. The increase in heritability was due to a reduction in the residual variance, albeit the rate of reduction in residual variance declined with each additional panellist included in the calculated mean tenderness score. Results highlight the importance of reporting the number of panellist scores per animal as well as their inter-correlations in sensory-based studies.

Rapid Communication: Large exploitable genetic variability exists to shorten age at slaughter in cattle.

Apprehension among consumers is mounting on the efficiency by which cattle convert feedstuffs into human edible protein and energy as well as the consequential effects on the environment. Most (genetic) studies that attempt to address these issues have generally focused on efficiency metrics defined over a certain time period of an animal's life cycle, predominantly the period representing the linear phase of growth. The age at which an animal reaches the carcass specifications for slaughter, however, is also known to vary between breeds; less is known on the extent of the within-breed variability in age at slaughter. Therefore, the objective of the present study was to quantify the phenotypic and genetic variability in the age at which cattle reach a predefined carcass weight and subcutaneous fat cover. A novel trait, labeled here as the deviation in age at slaughter (DAGE), was represented by the unexplained variability from a statistical model, with age at slaughter as the dependent variable and with the fixed effects, among others, of carcass weight and fat score (scale 1 to 15 scored by video image analysis of the carcass at slaughter). Variance components for DAGE were estimated using either a 2-step approach (i.e., the DAGE phenotype derived first and then variance components estimated) or a 1-step approach (i.e., variance components for age at slaughter estimated directly in a mixed model that included the fixed effects of, among others, carcass weight and carcass fat score as well as a random direct additive genetic effect). The raw phenotypic SD in DAGE was 44.2 d. The genetic SD and heritability for DAGE estimated using the 1-step or 2-step models varied from 14.2 to 15.1 d and from 0.23 to 0.26 (SE 0.02), respectively. Assuming the (genetic) variability in the number of days from birth to reaching a desired carcass specifications can be exploited without any associated unfavorable repercussions, considerable potential exists to improve not only the (feed) efficiency of the animal and farm system but also the environmental footprint of the system. The beauty of the approach proposed, relative to strategies that select directly for the feed intake complex and enteric methane emissions, is that data on age at slaughter are generally readily available. Of course, faster gains may potentially be achieved if a dual objective of improving animal efficiency per day coupled with reduced days to slaughter was embarked on.

The impact of multi-generational genotype imputation strategies on imputation accuracy and subsequent genomic predictions.

The objective of the present study was to quantify, using simulations, the impact of successive generations of genotype imputation on genomic predictions. The impact of using a small reference population of true genotypes versus a larger reference population of imputed genotypes on the accuracy of genomic predictions was also investigated. After construction of a founder population, high-density (HD) genotypes ( = 43,500 single nucleotide polymorphisms, SNP) were simulated across 25 generations ( = 46,800 per generation); a low-density genotype panel ( = 3,000 SNP) was developed from these HD genotypes, which was then used to impute genotypes using 7 alternative imputation strategies. Both low (0.03) and moderately (0.35) heritable phenotypes were simulated. Direct genomic values (DGV) were estimated using imputed genotypes from the investigated scenarios and the accuracy of predicting the simulated true breeding values (TBV) were expressed relative to the accuracy when the true genotypes were used. Mean allele concordance rate and the rate of change in mean allele concordance per generation differed between the imputation strategies investigated. Imputation was most accurate when the true HD genotypes of sires and 50% of the dams of the generation being imputed were included in the reference population; the average allele concordance rate for this scenario across generations was 0.9707. The strongest correlation between the TBV and DGV of the last generation was when the reference population included sequentially imputed HD genotypes of all previous generations, plus the true HD genotypes of all sires of the previous generations (0.987 as efficient as when the true genotypes were used in the reference population). With a moderate heritability, the correlation between the TBV and the DGV using a small reference population of accurate genotypes were, on average, 0.07 units stronger compared to DGV generated using a larger population of imputed genotypes. When the heritability was low, the accuracy of genomic predictions benefited from a larger reference population, even if SNP were imputed. The impact on the accuracy of genomic predictions from the accumulation of imputation errors across generations indicates the need to routinely generate HD genotypes on influential animals to reduce the accumulation of imputation errors over generations.

Ultra-low-density genotype panels for breed assignment of Angus and Hereford cattle.

Angus and Hereford beef is marketed internationally for apparent superior meat quality attributes; DNA-based breed authenticity could be a useful instrument to ensure consumer confidence on premium meat products. The objective of this study was to develop an ultra-low-density genotype panel to accurately quantify the Angus and Hereford breed proportion in biological samples. Medium-density genotypes (13 306 single nucleotide polymorphisms (SNPs)) were available on 54 703 commercial and 4042 purebred animals. The breed proportion of the commercial animals was generated from the medium-density genotypes and this estimate was regarded as the gold-standard breed composition. Ten genotype panels (100 to 1000 SNPs) were developed from the medium-density genotypes; five methods were used to identify the most informative SNPs and these included the Delta statistic, the fixation (F st) statistic and an index of both. Breed assignment analyses were undertaken for each breed, panel density and SNP selection method separately with a programme to infer population structure using the entire 13 306 SNP panel (representing the gold-standard measure). Breed assignment was undertaken for all commercial animals (n=54 703), animals deemed to contain some proportion of Angus based on pedigree (n=5740) and animals deemed to contain some proportion of Hereford based on pedigree (n=5187). The predicted breed proportion of all animals from the lower density panels was then compared with the gold-standard breed prediction. Panel density, SNP selection method and breed all had a significant effect on the correlation of predicted and actual breed proportion. Regardless of breed, the Index method of SNP selection numerically (but not significantly) outperformed all other selection methods in accuracy (i.e. correlation and root mean square of prediction) when panel density was ⩾300 SNPs. The correlation between actual and predicted breed proportion increased as panel density increased. Using 300 SNPs (selected using the global index method), the correlation between predicted and actual breed proportion was 0.993 and 0.995 in the Angus and Hereford validation populations, respectively. When SNP panels optimised for breed prediction in one population were used to predict the breed proportion of a separate population, the correlation between predicted and actual breed proportion was 0.034 and 0.044 weaker in the Hereford and Angus populations, respectively (using the 300 SNP panel). It is necessary to include at least 300 to 400 SNPs (per breed) on genotype panels to accurately predict breed proportion from biological samples.

Evaluation of developed low-density genotype panels for imputation to higher density in independent dairy and beef cattle populations.

The objective of this study was to develop, using alternative algorithms, low-density SNP genotyping panels (384 to 12,000 SNP), which can be accurately imputed to higher-density panels across independent cattle populations. Single nucleotide polymorphisms were selected based on genomic characteristics (i.e., linkage disequilibrium [LD], minor allele frequency [MAF], and genomic distance) in a population of 1,267 Holstein-Friesian animals genotyped on the Illumina Bovine50 Beadchip (54,001 SNP). Single nucleotide polymorphism selection methods included 1) random; 2) equidistant location; 3) combination of SNP MAF and LD structure while maintaining relatively equal genomic distance between adjacent SNP; 4) a combination of high MAF, genomic distance between selected and candidate SNP, and correlation between genotypes of selected and candidate SNP; and 5) a machine learning algorithm. The panels were validated separately in 1) a population of 750 Holstein-Friesian animals with masked genotypes to reflect the lower-density SNP densities under investigation (1,249 animals with complete genotypes included in reference population) and 2) a population of 359 Limousin and Charolais cattle with high (777,962 SNP)-density genotypes (1,918 animals with complete genotypes included in the reference population). Irrespective of SNP selection method, imputation accuracy in both populations improved at a diminishing rate as the number of SNP included in the lower-density genotype panel increased. Additionally, the variability in mean imputation accuracy per individual decreased as the panel density increased. The SNP selection method had a major impact on the mean allele concordance rate, although its impact diminished as the panel density increased. Imputation accuracy for SNP selected using a combination of high SNP MAF, LD structure, and relatively equal genomic distance between SNP outperformed all other selection methods in densities < 12,000 SNP. Using this method of SNP selection, the correlation between the imputed and actual genotypes for the 3,000 SNP panel was 0.90 and 0.96 when applied to the beef and dairy populations, respectively; the respective correlations for the 6,000 SNP panel were 0.95 and 0.98. It is necessary to include between 3,000 and 6,000 SNP in a low-density panel to achieve adequate imputation accuracy to either medium density (approximately 50,000 SNP in the dairy population) or high density (approximately 700,000 SNP in the beef population) across diverse and independent populations.

A novel mutation in IL36RN underpins childhood pustular dermatosis.

BACKGROUND: Chronic pustular dermatoses are severe and debilitating autoinflammatory conditions that can have a monogenic basis. Their clinical features are, however, complex with considerable overlap. Null and missense mutations in the genes encoding interleukin (IL)-1 family (IL-1 and IL-36) anti-inflammatory receptor antagonist (Ra) cytokines can underlie the development of severe pustular dermatoses. OBJECTIVE: We present a clinical and genetic study of four children of Pakistani descent with similar clinical presentations and treatment course, each of whom suffers from a severe pustular dermatosis, initially described as a pustular variant of psoriasis. We use DNA sequencing to refine the diagnosis of two of the children studied. METHODS: Bidirectional Sanger sequencing was performed on the coding regions of the IL-1Ra and IL-36Ra genes (IL1RN and IL36RN, respectively), for the four affected children and their parents. RESULTS: We identified a novel homozygous missense mutation in IL36RN in two siblings, and showed the molecular basis of the condition to be both distinct from psoriasis and distinct between the two families studied. CONCLUSIONS: We describe a novel mutation which underpins the diagnosis of childhood pustular dermatosis. Molecular diagnostics can be used to aid the clinical diagnosis and potential treatment of autoinflammatory conditions.

Scatter radiation intensities around full-field digital mammography units.

The aim of this study was to investigate the scatter radiation intensity around digital mammography systems and apply these data to standard shielding calculations to reveal whether shielding design of existing breast screening rooms is adequate for the use of digital mammography systems. Three digital mammography systems from GE Healthcare, Hologic and Philips were employed in the study. A breast-equivalent phantom was imaged under clinical workload conditions and scatter radiation intensities around the digital mammography systems were measured for a range of angles in three planes using an ionisation chamber. The results were compared with those from previous studies of film-screen systems. It may be deduced from the results that scattering in the backward direction is significant for all three systems, while scattering in the forward direction can be significant for some planes around the GE and Hologic systems. Measurements at typical clinical settings on each system revealed the Philips system to have markedly lower scatter radiation intensities than the other systems. Substituting the measured scattered radiation intensity into shielding calculations yielded barrier requirements similar to those already in place at the screening centres operating these systems. Current radiation protection requirements based on film-screen technology remain sufficient when applied to rooms with digital mammography installations and no alteration is required to the structural shielding.

ResearchTracking: Monitoring gender and ethnic minority recruitment and retention in cancer symptom studies.

BACKGROUND: Recruiting and retaining participants for clinical trials, particularly women and ethnic minorities, are challenging. Few studies, however, examine gender and ethnic differences in research processes. Such information is important for findings to adequately represent the available population. OBJECTIVE: The study aim was to examine study recruitment processes (referral, eligibility, consent/enrollment) and study retention (completion) for gender and ethnic differences. METHODS: A descriptive comparative analysis of data from 2 randomized clinical trials focused on cancer outpatients with pain and/or fatigue. A computerized ResearchTracking software allowed documentation of recruitment and retention effort outcomes. RESULTS: Among the 1464 referred patients, 612 (42%) were eligible for study participation. Lack of ongoing care at the study settings and lack of English skills were the main reasons for ineligibility. There were no gender differences in consent/enrollment or completion rates. Ethnic minority patients were represented proportionally to the available population (13%) and were equally willing to consent/enroll and complete both studies as their white counterparts, if they were eligible. CONCLUSIONS: Specific strategies to target language eligibility barriers are necessary to increase minority participation. IMPLICATIONS FOR PRACTICE: Future studies could include audio-aided tools in their native language to help recruit patients with limited English skills, if the study tools can be validly translated into other languages and are equivalent to English versions. Efforts to educate and garner support of providers could improve enrollment of patients in cancer studies, especially in studies of audio- or video-recorded patient-provider interaction.

UV inhibits allergic airways disease in mice by reducing effector CD4 T cells.

BACKGROUND: In human asthma, and experimental allergic airways disease in mice, antigen-presenting cells and CD4(+) effector cells at the airway mucosa orchestrate, and CD4(+)CD25(+) regulatory T cells attenuate, allergen immunity. UV irradiation of skin before sensitization with ovalbumin (OVA) causes significantly reduced asthma-like responses in respiratory tissues. OBJECTIVE: To determine whether UV-induced changes in CD11c(+) cells, CD4(+)CD25(+) effector cells or CD4(+)CD25(+) regulatory cells in the trachea and airway draining lymph nodes (ADLNs) were responsible for reduced allergic airways disease. METHODS: The phenotype and function of CD11c(+) cells and CD4(+)CD25(+) cells in the trachea and ADLNs of UV- and non-irradiated, OVA-sensitized mice was examined 24 h after a single exposure to aerosolized OVA. RESULTS: No changes in the function of CD11c(+) cells from UV-irradiated mice were observed. CD4(+)CD25(+) cells from UV-irradiated, OVA-sensitized mice harvested 24 h after OVA aerosol proliferated less in response to OVA in vitro and were unable to suppress the proliferation of OVA-sensitized responder cells. This result suggested reduced activation of effector T cells in the airway mucosa of UV-irradiated, OVA-sensitized mice. To exclude regulatory cells of any type, there was similar proliferation in vivo to aerosolized OVA by CFSE-loaded, OVA-TCR-specific CD4(+) cells adoptively transferred into UV- and non-irradiated, OVA-sensitized mice. In addition, there was no difference in the expression of regulatory T cell markers (Foxp3, IL-10, TGF-beta mRNA). To examine effector T cells, ADLN cells from UV-irradiated, OVA-sensitized and -challenged mice were cultured with OVA. There was reduced expression of the early activation marker CD69 by CD4(+)CD25(+) cells, and reduced proliferation in the absence of the regulatory cytokine, IL-10. CONCLUSION: Reduced allergic airways disease in UV-irradiated mice is due to fewer effector CD4(+)CD25(+) cells in the trachea and ADLNs, and not due to UV-induced regulatory cells.

Lifelong scaling and blistering in a family.

Ichthyosis bullosa of Siemens is a genodermatosis, which presents in childhood with mild blistering and hyperkeratosis. The heterogeneous clinical presentation may lead to misdiagnosis, even in the presence of a strong family history. Genetic testing and counselling may help in diagnosis and treatment.

Responses to the cannabinoid receptor-1 antagonist, AM251, are more robust with age and with high-fat feeding.

Endocannabinoids (EC) are involved in regulating energy homeostasis, particularly in promoting hyperphagia and the consumption of a palatable diet. We have previously shown that rats given a high-fat (HF) diet display a transient hyperphagia that is normalized by a process partially dependent on leptin. We now propose that the induction of this hyperphagia is mediated, at least partially, by the EC signaling system. Obesity, including diet-induced and age-related, is associated with dysregulation of the EC system, and obese rodent models are hypersensitive to a cannabinoid-1 (CB1) receptor antagonist. This suggests that aged rats will be more responsive to the anorectic effects of a CB1 receptor antagonist. To test this, we examined the responsiveness to CB1 receptor antagonist, AM251, in young and aged rats during two experimental paradigms. First, we administered AM251 simultaneously with the introduction of an HF diet. Second, AM251 treatment began after the establishment of diet-induced obesity. Responses were measured by changes in body weight and composition, calorie intake, serum leptin, and biochemical indicators. The results demonstrated three key findings. 1) CB1 receptor activity contributes to the hyperphagia seen with the introduction of an HF diet. 2) Increased AM251 sensitivity and efficacy is increased with age and HF feeding, with the greatest responsiveness observed in HF-fed, aged rats. 3) AM251 sensitivity is elevated to a greater extent with HF diet than with established obesity. Thus, both age and an HF diet are associated with enhanced anorectic responses to AM251, but the underlying mechanism of these responses remains speculative.