Preliminary Study of Body Temperature Emissivity in Rabbits Selected for Litter Size Residual Variability

A divergent selection for litter size residual variability has been carried out in rabbits during 12 generations. Litter size residual variability was estimated as phenotypic variance of litter size within females after correcting for the year-season and the parity-lactation status effects. Stress causes an increase in core body temperature. Infrared thermography (IRT) has been shown to be a useful technique for identifying changes in body temperature emissivity. The aim of this work is to study the correlated response to selection for litter size residual variability in body temperature emissivity at natural mating. Natural mating can be considered a stressful stimulus for does. Temperature was measured in the eyeball by IRT before mating (basal temperature) and after 5 min, 30 min, and 60 min in does of the lines selected to decrease and to increase litter size residual variability (i.e., the Low and the High lines). Both lines showed similar basal temperature. Eyeball temperature was increased slightly in the Low line from basal state to 5 min after stressful stimulus (from 35.69 °C to 36.32 °C), and this increase remained up to 60 min after stress (36.55 °C). The High line showed a higher temperature than the Low line at 30 min (+0.96 °C, p = 0.99). At 60 min, temperature was similar between lines. The evolution of temperature was different between lines: the High line reached the peak of temperature later than the Low line (at 30 min vs. 5 min), and its peak was higher compared to the Low line (36.95 °C vs. 36.32 °C). In conclusion, the does selected for reducing litter size variability showed a lower increase in temperature after a stressful stimulus, therefore showing lower stress and consequently better welfare.

Correlated Response to Selection for Litter Size Residual Variability in Rabbits’ Body Condition

A divergent selection experiment for residual variance of litter size at birth was carried out in rabbits during twelve generations. Residual variance of litter size was estimated as the within-doe variance of litter size after pre-correction for year and season as well as parity and lactation status effects. The aim of this work was to study the correlated response to selection for litter size residual variability in body condition from mating to weaning. Body condition is related directly to an animal’s fat deposits. Perirenal fat is the main fat deposit in rabbits. Individual body weight (IBW) and perirenal fat thickness (PFT) were used to measure body condition at second mating, delivery, 10 days after delivery, and weaning. Litter size of the first three parities was analyzed. Both lines decreased body condition between mating to delivery; however, the decrease in body condition at delivery was lower in the low line, despite this line having higher litter size at birth (+0.54 kits, p = 0.93). The increment of body condition between delivery and early lactation was slightly higher in the low line. On the other hand, body condition affected success of females’ receptivity and fertility at the third mating, e.g., receptive females showed a higher IBW and PFT than unreceptive ones (+129 g and +0.28 mm, respectively), and fertile females had a higher IBW and PFT than unfertile ones (+82 g and +0.28 mm, respectively). In conclusion, the does selected for reducing litter size variability showed a better deal with situations of high-energy demand, such as delivery and lactation, than those selected for increasing litter size variability, which would agree with the better health and welfare condition in the low line.

Evaluating Facility Characteristics and Connectivity Metrics as Predictors of Clostridioides difficile Rates in Nursing Homes, Atlanta, GA

Background: Nursing home (NH) residents are at high risk for Clostridioides difficile infection (CDI) due to older age, frequent antibiotic exposure, and previous healthcare exposure. Incidence of CDI attributed to NHs is not well established, but it is hypothesized to be related to the magnitude of transfers. We evaluated the relationship between NH CDI incidence and facility characteristics to explain variability in rates in Atlanta, Georgia. Methods: Incident C. difficile cases from 2016 to 2018 were identified through the Georgia Emerging Infections Program (funded by the Centers for Disease Control and Prevention), which conducts active population-based surveillance in the 8-county metro Atlanta area. An incident case was defined as an NH resident with a toxin-positive stool specimen (without a positive test within 8 weeks). Sampled (1 to 3 on age and gender) incident cases were attributed to a NH if a patient was an NH resident within 4 days of specimen collection. Facility characteristics (beds, resident days, admissions, and average length of stay [ALOS]) were obtained from NH cost reports, and facility-specific connectivity metrics were calculated (indegree and betweenness) from 2016 Medicare claims data. Case counts were aggregated to estimate yearly incidence and correlated with facility characteristics and location within the healthcare network using the Spearman correlation. A negative binomial model was used to assess residual variability in NH CDI incidence. Results: In total, 386 incident CDI cases were attributed to 64 NHs (range, 0–27). Approximately half (54.7%) resided in the NH at the time of specimen collection; however, 33.7% were in inpatient units (≤4 days of admission), and 10.9% were in an emergency room (ER). The frequency of NH CDI cases correlated strongly with admissions (r = .70; P < .01), inversely with ALOS (r = −0.53; P < .01), and moderately with resident days (r = .38; P < .01). After accounting for admissions, incidence (per 1,000 admissions) still varied (Fig. 1) (median 14; range, 0–34). The inverse association with ALOS decreased and incidence no longer correlated with the remaining facility characteristics or location within the healthcare transfer network (P > .05, all comparisons). However, there was residual correlation with connectivity metrics (indegree r = 0.26; P = .04). Conclusions: Our data suggest that attributing CDI to NHs requires the inclusion of hospital and ER-based specimen collection. NH CDI incidence appears highest among facilities with a low ALOS and a high number of admissions; incidence rates calculated per 1,000 admissions may best account for infection risk inherent early in a resident’s stay. Residual variability attributed to connectivity to the healthcare network was of borderline significance and should be further explored in the NH setting.Funding: NoneDisclosures: Scott Fridkin, consulting fee, vaccine industry (spouse)

Atmospheric Internal Variability in the Summer Indo–Northwestern Pacific: Role of the Intraseasonal Oscillation

Summer atmospheric interannual variability in the Indo–northwestern Pacific (NWP) is coupled with tropical sea surface temperature (SST) variability. This study investigates the importance and origin of atmospheric internal variability in the Indo-NWP region. Using the reanalysis and the 30-member atmospheric model simulation, two SST-related interannual modes are identified in the Indo-NWP region during boreal summer with the month-reliant empirical orthogonal function analysis. The first mode is related to concurrent El Niño–Southern Oscillation originating from the eastern equatorial Pacific whereas the second mode features an anomalous anticyclone (AAC) in post–El Niño summers over the NWP region, known as the Indo-western Pacific Ocean capacitor. The SST-induced modes show temporal persistence from June to August. The residual variability is the focus of this study. The dominant mode of the residual variability displays an AAC structure over the NWP but little month-to-month persistence, indicative of atmospheric internal dynamics unrelated to SST forcing. Further investigation suggests the monthly internal AAC arises from the summer intraseasonal oscillation (ISO). The broad band of ISO yields nonzero monthly means that project strongly onto the AAC pattern. Finally, the anomalies of rainfall and low-level circulation in summer 2016 are investigated. The reversal of the low-level circulation pattern from an AAC in July to an anomalous cyclone over the NWP in August 2016 is due to the ISO-induced internal variability.

Race/Ethnicity and Protease Inhibitor Use Influence Plasma Tenofovir Exposure in Adults Living with HIV-1 in AIDS Clinical Trials Group Study A5202

ABSTRACT AIDS Clinical Trial Group study A5202 (ClinicalTrials.gov identifier NCT00118898) was a phase 3b, randomized, partially blinded equivalence study of open-label atazanavir/ritonavir or efavirenz, plus either placebo-controlled tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine, in treatment-naive adults living with HIV-1, evaluating efficacy, safety, and tolerability. We report an analysis of the contribution of participant characteristics to the disposition of tenofovir plasma concentrations. Tenofovir concentration data from a total of 817 individuals (88% of the total number of eligible patients randomly assigned to receive treatment in the TDF-containing arms of A5202) were available for analysis. Pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. One- and two-compartment models with first-order absorption and first-order elimination were evaluated. An exponential error model was used for examination of interindividual variability (IIV), and a proportional and mixed-error model was assessed for residual variability. The final structural model contained two compartments with first-order absorption and elimination. IIV was estimated for apparent clearance (CL/F) and the first-order absorption rate constant (ka), and a proportional residual variability model was selected. The final mean parameter estimates were as follows: ka = 2.87 h−1, CL/F = 37.2 liters/h, apparent volumes of the central and peripheral compartments = 127 and 646 liters, respectively, and apparent intercompartmental clearance = 107 liters/h. In addition to race/ethnicity, creatinine clearance and assignment to atazanavir/ritonavir or efavirenz were significantly associated with CL/F (P < 0.001). In conclusion, race/ethnicity is associated with tenofovir oral CL in HIV-1 positive, treatment-naive adults. This covariate relationship raises questions about the possibility of differences in efficacy and risk of adverse events in different patient populations and suggests that examining preexposure prophylaxis regimens and tenofovir exposure in different race/ethnicity groups be considered.

Density-dependence can be revealed by modelling the variance in the stock–recruitment process: an application to flatfish

Recruitment success in marine species is mostly driven by the high and variable mortality of first life stages, and the relationships between stock and recruitment are then largely dominated by residual variability. We show that analysing the residual variability may provide insights on the density-dependence process occurring during the recruitment. Following the seminal formulation of Minto et al. (Survival variability and population density in fish populations. Nature, 2008), we show that when recruitment is considered as a sequence of a pelagic stage with stochastic density-independent mortality followed by a second stage with stochastic density-dependent mortality, then the variability of the recruitment rate per spawning biomass (RPSB) should be a decreasing function of the spawning biomass. Using stock–recruit data of 148 stocks from the RAM legacy database, we provide a test of this hypothesis by showing that the variability of RPSB is lower for fish species with the higher concentration during juvenile stages. Second, a hierarchical Bayesian model (HBM) is built to derive a meta-analysis of stock–recruit data for 39 flatfish stocks, characterized by a high concentration of juveniles in coastal nursery habitats. Results of the HBM show that the variance of the RPSB decreases with the spawning biomass for almost all stocks, thus providing strong evidence of density-dependence during the recruitment process. Finally, we attempt to relate patterns in recruitment variance to relevant life-history traits of flatfish species.

Multiphasic growth models for cattle

There are several ways of generalizing classical growth models to describe the complex nature of animal growth. One possibility is to construct a model based on a sum of several classical growth functions. In this paper, such multiphasic growth models for breeding bulls of the Czech Pied cattle based on the sum of two logistic functions are studied. The logistic function was chosen as a base for the models due to the relatively low degree of nonlinearity for the growth data. The paper describes three steps of constructing such a multiphasic growth model: in the first step a model with four unknown parameters is considered, in the second step the number of model parameters which are to be estimated is increased to five and in the third step a general model with six parameters is used. In each step, statistical properties of the considered model are checked. The residual variability of the best fitting model is on average approx. 8 times lower than the residual variability of classical Gompertz model which is often used by breeders to model cattle growth. &nbsp;

Population Pharmacokinetic Model of ADVATE in Pediatric and Adult Patients with Hemophilia A.

Abstract 3492 Poster Board III-429 Introduction The objective of this analysis was to characterize the population pharmacokinetic (PK) model of ADVATE® (Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method) in hemophilia A patients. This included estimation of typical population pharmacokinetic parameters and inter-individual and residual variability and identification of covariates that are significant predictors of variability in a pooled population of children and adults. Patients and Methods Plasma FVIII activity PK data were collected for 3 ADVATE® clinical trials in previously treated patients: 184 full PK data sets for 100 adults/adolescents, aged 10 to 65 years, and from 52 reduced sample PK data sets for 52 children, aged 1 to 6 years. Population PK analysis was conducted using non-linear mixed effects modeling with the first-order integral approximation method in SAS® software (NLMIXED procedure). A two-compartment model was used as the base model and the influence of age and weight were explored. Results Two-compartment PK models with additive plus proportional residual variability model and exponential inter-individual variability model adequately described the data. Clearance (CL) is significantly correlated with age and body weight and central volume of distribution (V1) is also related with body weight. The estimated population PK parameters were (mean parameter, (inter-individual variability %)): CL (2.92 mL/kg·h, 22%), V1 (0.46 dL/kg, 5.2%), peripheral volume V2 (0.09 dL/kg) and inter-compartmental clearance Q (2.07 mL/ kg·h). Conclusions A population PK model that describes the combined PK data from adults and pediatric studies has been constructed. A significant portion of inter-individual variability in both volume and clearance can be explained by subject weight. An additional smaller effect of age on clearance but not volume was observed. A population PK model for Factor VIII could provide the clinician with advantages in designing a patient specific treatment regimen. It could provide more relevant guidance in individual patient pharmacokinetics than just incremental recovery without the burden of a full PK assessment of the patient. Disclosures: Oh: Baxter: Employment. Off Label Use: Prophylaxis is not indicated in the US. Björkman:Baxter: Consultancy; Octapharma: Consultancy. Schroth:Baxter: Employment. Fritsch:Baxter: Employment. Collins:Bayer: Consultancy; Novo Nordisk: Consultancy; Baxter: Consultancy. Fischer:Bayer: Consultancy; Wyeth: Consultancy; Baxter: Consultancy. Blanchette:Bayer: Consultancy; Baxter: Consultancy. Casey:Baxter: Employment. Spotts:Baxter: Employment. Ewenstein:Baxter: Employment.