Risk maps summarizing landscape suitability of novel areas for invading species can be valuable tools for preventing species’ invasions or controlling their spread, but methods employed for ...development of such maps remain variable and unstandardized. We discuss several considerations in development of such models, including types of distributional information that should be used, the nature of explanatory variables that should be incorporated, and caveats regarding model testing and evaluation. We highlight that, in the case of invasive species, such distributional predictions should aim to derive the best hypothesis of the potential distribution of the species by using (1) all distributional information available, including information from both the native range and other invaded regions; (2) predictors linked as directly as is feasible to the physiological requirements of the species; and (3) modelling procedures that carefully avoid overfitting to the training data. Finally, model testing and evaluation should focus on well-predicted presences, and less on efficient prediction of absences; a k-fold regional cross-validation test is discussed.
It is standard practice in preclinical biomedical research to house mammalian model organisms at an ambient temperature substantially below the thermoneutral zone. These experimental studies are ...performed using animals that are chronically challenged by mild cold stress. This condition increases food intake, metabolic rate, sympathetic activity, blood pressure and heart rate. Furthermore, this condition alters the behavioral and physiological responses to drug administration, energy restriction and overfeeding. This paper will review these observations, which must be understood in the context of phenotyping small mammals to enhance our understanding of the biology of human disease.
The association between negative energy balance and health has led to the testing of blood analytes such as nonesterified fatty acids (NEFA) to identify opportunities for improving the management of ...transition dairy cows. The objective of this study was to evaluate whether prepartum analytes associated with stress (cortisol) or inflammation (haptoglobin) could also identify dairy cattle at increased risk for health complications after calving. Prepartum blood and fecal samples were collected once weekly from 412 Holstein dairy cows on 2 commercial dairy farms (at wk −3, −2, and −1 relative to calving) and analyzed for concentrations of NEFA, haptoglobin (Hp), and cortisol in plasma and cortisol metabolites in feces. Retained placenta (RP), displaced abomasum (DA), subclinical ketosis (SCK), high Hp concentration (HiHp), and death were recorded up to 30 d in milk (DIM), and animals were subsequently categorized into 3 health categories: (1) no disorder of interest (NDI); (2) one disorder (RP, DA, SCK, or HiHp); or (3) more than one disorder (RP, DA, SCK, HiHp) or death. With the exception of prepartum NEFA, no associations were detected between prepartum concentrations of our analytes of interest and the occurrence of one disorder (RP, DA, SCK, or HiHP) by 30 DIM. Haptoglobin concentration tended to be greater during wk −2 and −1 in cows that developed more than one disorder or that died by 30 DIM; however, when calving assistance was included as a covariate in the analysis prepartum, Hp was no longer a significant risk factor for this postpartum health outcome. Primiparous cows with plasma cortisol concentrations >22.2nmol/L during wk −2 had reduced odds odds ratio (OR) 0.41; 95% confidence interval (CI) 0.17–0.98 of developing more than one disorder or death by 30 DIM, whereas multiparous cows with plasma cortisol >34.1nmol/L during wk −2 tended to have greater odds (OR 2.53; 95% CI 0.87–7.37) of developing more than one disorder or death by 30 DIM. Individual variation in daily cortisol secretion patterns and stress responses to the restraint and handling associated with sample collection make prepartum plasma cortisol data and its relationship to postpartum health difficult to interpret. Among multiparous cows, for every 500-unit (ng/g of fecal dry matter) increase in fecal cortisol metabolite concentration during wk −2, cows had increased odds (OR 1.41; 95% CI 1.12–1.79) of developing more than one disorder or dying after calving. For multiparous cows, every 0.15mmol/L increase in plasma NEFA concentration during any of the 3 wk before calving was associated with an approximately 2-fold increase in the odds of developing more than one disorder or dying by 30 DIM. Fecal cortisol metabolite concentration during the prepartum period did not predict which cows would go on to develop more than one disorder or die within 30 DIM as accurately as prepartum NEFA concentration; therefore, this analyte is not a suitable substitute for NEFA for assessing opportunities to improve herd health.
The objective of this study was to evaluate the association of postpartum plasma Ca concentration with early-lactation disease outcomes, culling within 60 d in milk, pregnancy to first service, and ...milk production. A total of 1,453 cows from 5 commercial dairy farms in New York State were enrolled in a prospective cohort study from February to November 2015. Blood samples were collected within 12 h of parturition, and plasma was submitted to a diagnostic laboratory for total Ca measurement. Early-lactation disease, reproductive performance, and milk production from Dairy Herd Improvement Association (DHIA) test-day data were compiled from each farm's management software. Multivariable Poisson regression models were built to evaluate the association of plasma Ca with the risks of retained placenta (RP), metritis, displaced abomasum (DA), clinical mastitis, culling within 60 d in milk, and pregnancy to first service. Repeated-measures ANOVA were used to evaluate the association of Ca at parturition with milk production across the first 9 DHIA tests. Herd was considered a random effect in all models. Primiparous cows were modeled separately from multiparous cows if differential responses were observed. Calcium was not associated with the risk of RP, metritis, clinical mastitis, or pregnancy to first service in primiparous or multiparous cows. For multiparous cows only, higher Ca concentration tended to be associated with increased culling within the first 60 d in milk. Multiparous cows with Ca ≤1.85 mmol/L had an increased risk of being diagnosed with a DA compared with cows with Ca >1.85 mmol/L. For the milk production models, Ca was not associated with the amount of milk produced within the first 9 DHIA tests in primiparous cows; however, multiparous cows with Ca ≤1.95 mmol/L produced, on average, 1.1 kg more milk per day across the 9 DHIA tests than their multiparous counterparts with Ca >1.95 mmol/L. Our results indicate that plasma Ca concentration measured within 12 h of parturition is a poor predictor of early-lactation health outcomes. Reduced Ca concentration in the immediate postpartum period was associated with higher milk production in multiparous cows. From these results, we caution that studies attempting to categorize subclinical hypocalcemia based on a single sample in the immediate postpartum period could misclassify the disorder.
It is generally accepted that cardiac sympathetic tone dominates the control of heart rate (HR) in mice. However, we have recently challenged this notion given that HR in the mouse is responsive to ...ambient temperature (T(a)) and that the housing T(a) is typically 21-23 degrees C, well below the thermoneutral zone ( approximately 30 degrees C) of this species. To specifically test the hypothesis that cardiac sympathetic tone is the primary mediator of HR control in the mouse, we first examined the metabolic and cardiovascular responses to rapid changes in T(a) to demonstrate the sensitivity of the mouse cardiovascular system to T(a). We then determined HR in 1) mice deficient in cardiac sympathetic tone ("beta-less" mice), 2) mice deficient in cardiac vagal tone muscarinic M(2) receptor (M(2)R(-/-)) mice, and 3) littermate controls. At a T(a) of 30 degrees C, the HR of beta-less mice was identical to that of wild-type mice (351 +/- 11 and 363 +/- 10 beats/min, respectively). However, the HR of M(2)R(-/-) mice was significantly greater (416 +/- 7 beats/min), demonstrating that vagal tone predominates over HR control at this T(a). When these mice were calorically restricted to 70% of normal intake, HR fell equally in wild-type, beta-less, and M(2)R(-/-) mice (DeltaHR = 73 +/- 9, 76 +/- 3, and 73 +/- 7 beats/min, respectively), suggesting that the fall in intrinsic HR governs bradycardia of calorically restricted mice. Only when the T(a) was relatively cool, at 23 degrees C, did beta-less mice exhibit a HR (442 +/- 14 beats/min) that was different from that of littermate controls (604 +/- 10 beats/min) and M(2)R(-/-) mice (602 +/- 5 beats/min). These experiments conclusively demonstrate that in the absence of cold stress, regulation of vagal tone and modulation of intrinsic rate are important determinants of HR control in the mouse.
A farm-level stochastic simulation model was modified to estimate the cost per case of 3 foot disorders (digital dermatitis, sole ulcer, and white line disease) by parity group and incidence timing. ...Disorder expenditures considered within the model included therapeutics, outside labor, and on-farm labor. Disorder losses considered within the model included discarded milk, reduced milk production, extended days open, an increased risk of culling, an increased risk of death (natural or euthanized), and disease recurrence. All estimates of expenditures and losses were defined using data from previously published research in stochastic distributions. Stochastic simulation was used to account for variation within the farm model; 1,000 iterations were run. Sensitivity of foot disorder costs to selected market prices (milk price, feed price, replacement heifer price, and slaughter price) and herd-specific performance variables (pregnancy rate) were analyzed. Using our model assumptions, the cost per disorder case over all combinations of parity group and incidence timing, regardless of incidence likelihood, was lowest for digital dermatitis ($64 ± 24; mean ± standard deviation), followed by white line disease ($152 ± 26) and sole ulcer ($178 ± 29). Disorder costs were greater in multiparous versus primiparous cows and were always highest at the beginning of lactation. The greatest contributing cost categories were decreased milk production, an increased risk of culling, and disease recurrence. The contribution of cost categories to the total cost of disorder varied by disorder type, parity group, and incidence timing. For all disorders, the cost per case increased as milk price or replacement heifer price increased and decreased as feed price, pregnancy rate, or slaughter price increased. Understanding how foot disorder costs change according to cow-specific conditions (i.e., disorder type, parity group, and days in milk at incidence) and herd-specific conditions (i.e., market prices and performance variables) can help improve on-farm decisions about treatment and prevention of foot disorders.
Our objectives were to determine (1) the effect of a single dose of an oral Ca bolus within 24 h after parturition on plasma Ca concentration, (2) the response of primiparous (PP) and multiparous ...(MP) cows to this supplementation strategy, and (3) differential responses based on plasma Ca at enrollment. For objective 1, cows from 1 commercial dairy in New York State were enrolled within 19 h after parturition (mean ± standard deviation = 8.3 ± 5.3 h) and randomized within parity group (first, second, and ≥third) to control CON (n = 25); no placebo or a single dose bolus treatment BOL (n = 25); 3 oral Ca boluses supplying 54 to 64 g of Ca. Plasma Ca was measured repeatedly between 1 and 24 h following treatment. For objectives 2 and 3, cows on 6 commercial farms in New York State were assigned to treatment as for objective 1 (CON, n = 1,973; BOL, n = 1,976). Herd records for health, reproduction, and Dairy Herd Improvement Association test day milk production were collected. Mixed effect multivariable models were developed using repeated measures ANOVA, Poisson regression, or proportional hazard models. Objective 2 analyses considered treatment with periparturient risk factors, whereas objective 3 analyses also considered Ca status. No difference was observed for plasma Ca between 1 and 24 h after treatment. Primiparous cows assigned to BOL calving at >712 d old had decreased risk of one or more health disorders ≤30 d in milk; risk ratio (RR) = 0.65, 95% confidence interval (CI) = 0.51 to 0.84 and those with body condition score >3.5 responded to BOL with increased milk production (CON = 31.7 ± 1.1, BOL = 35.1 ± 1.1 kg/d), as did those with days carried calf >277 (CON = 31.9 ± 1.0, BOL = 34.7 ± 1.0 kg/d). Reduced risk of one or more health disorders was observed in parity ≥3 (RR = 0.85, 95% CI = 0.81 to 0.89) and MP cows with body condition score >3.5 (retained placenta; RR = 0.70, 95% CI = 0.58 to 0.84) or that were lame (displaced abomasum; RR = 0.49, 95% CI = 0.32 to 0.75). Differential responses for PP cows by Ca status were minimal. For MP cows with low plasma Ca, BOL decreased risk of additional Ca treatment (≤1.8 mmol/L; RR = 0.57, 95% CI = 0.40 to 0.80) as well as risk of one or more health disorders (≤2.15 mmol/L; RR = 0.90, 95% CI = 0.85 to 0.95). Supplementation with a single oral dose of Ca could be targeted to periparturient risk groups for improved health. Calcium status did not differentiate responses of PP cows, but MP cows with low Ca at parturition had improved health status when supplemented.
The objectives of this study were to (1) compare a test for serum measurement of total Ca (tCa), Mg, and P (VetTest Chemistry Analyzer, IDEXX Laboratories Inc., Westbrook, ME) to reference methods ...(spectrophotometric assays on a Beckman Coulter 640e automated clinical chemistry analyzer; Beckman Coulter, Brea, CA), (2) determine the relationship between ionized Ca (iCa) and reference method tCa in the immediate postpartum period, and (3) assess the relative value of these blood Ca indices as predictors of neutrophil oxidative burst activity. Samples were collected from multiparous Holstein cows (n = 33) over the first 5 d in milk. A total of 183 samples for objective 1 and 181 samples for objective 2 were available. Neutrophil oxidative burst activity was assessed once between 2 and 5 d in milk (n = 29). Linear regression demonstrated strong relationships between serum tCa, Mg, and P concentrations measured by the VetTest compared with the reference method. Bland Altman analysis indicated that the VetTest values were higher than the reference method by 0.22 mmol/L for tCa, 0.12 mmol/L for Mg, and 0.16 mmol/L for P. Compared with hypocalcemia categorized at ≤2.0 or ≤2.125 mmol/L with the reference method tCa, thresholds for the VetTest measured tCa of ≤2.23 mmol/L (sensitivity = 87%, specificity = 89%) or ≤2.30 mmol/L (sensitivity = 86%, specificity = 96%) could be used. The relationship between whole-blood iCa and reference method serum tCa differed by sampling time point after calving. Compared with identification of hypocalcemia with serum tCa measurements from the reference method (thresholds of ≤2.0 and 2.125 mmol/L), a whole-blood iCa threshold of ≤1.17 mmol/L resulted in the highest combined sensitivities (94 and 82%) and specificities (80 and 94%) at either threshold. Ionized Ca measurements were more consistently related to outcomes of neutrophil oxidative burst activity measured in vitro. The VetTest measurements of serum tCa reliably identified hypocalcemia when thresholds were adjusted to account for the bias of the test. The variation in the relationship between iCa and reference method tCa in the days following parturition suggest that these measures cannot be used interchangeably as indicators of Ca status. The more consistent associations between iCa and in vitro measures of neutrophil function, compared with tCa, indicated that this may be a more sensitive predictor of functional outcomes associated with postpartum Ca status.
Background. The prevalence of and risk factors for abnormal anal cytology among men and women with human immunodeficiency virus (HIV) infection have not been extensively investigated. Methods. The ...Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN study) is a prospective cohort study of HIV-infected patients in 4 US cities. Baseline questionnaires were administered and anal samples for cytology and human papillomavirus (HPV) detection and genotyping were collected. Results. Among 471 men and 150 women (median age, 41 years), 78% of participants were receiving combination antiretroviral therapy, 41% had a CD4+ cell count of ⩾500 cells/µL, and 71% had an HIV RNA viral load of <400 copies/mL. The anal cytology results were as follows: 336 participants (54%) had negative results, 96 participants (15%) had atypical squamous cells, 149 participants (24%) had low-grade squamous intraepithelial lesions, and 40 participants (6%) had high-grade squamous intraepithelial lesions. In a multivariate analysis, abnormal anal cytology was associated with number of high-risk and low-risk HPV types (adjusted odds ratio AOR for both, 1.28; P = .001), nadir CD4+ cell count of <50 cells/µL (AOR, 2.38; P = .001), baseline CD4+ cell count of <500 cells/µL (AOR, 1.75; P = .004), and ever having receptive anal intercourse (AOR, 2.51; P < .001). Conclusion. HIV-infected persons with multiple anal HPV types or a nadir CD4+ cell count of <50 cells/µL have an increased risk for abnormal anal cytology.
Objective: Gene-targeted deletion of the voltage-gated potassium channel, Kv1.3, results in 'super-smeller' mice that have altered firing patterns of mitral cells in the olfactory bulb, modified ...axonal targeting to glomerular synaptic units, and behaviorally have an increased ability to detect and discriminate odors. Moreover, the Kv1.3-null mice weighed less than their wild-type counterparts, have modified ingestive behaviors, and are resistant to fat deposition following a moderately high-fat dietary regime. In this study, we investigate whether or not gene-targeted deletion of Kv1.3 (Shaker family member) can abrogate weight gain in a genetic model of obesity, the melanocortin-4 receptor-null mouse (MC4R-null). Design: Mice with double gene-targeted deletions of Kv1.3 and MC4R were generated by interbreeding Kv1.3 (Kv)- and MC4R-null mouse lines to homozygosity. Developmental weights, nose to anus length, fat pad weight, fasting serum chemistry, oxygen consumption, carbon dioxide respiration, locomotor activity and caloric intake were monitored in control, Kv-null, MC4R-null and Kv/MC4R-null mice. Physiological and metabolic profiles were acquired at postnatal day 60 (P60) in order to explore changes linked to body weight at the reported onset of obesity in the MC4R-null model. Results: Gene-targeted deletion of Kv1.3 in MC4R-null mice reduces body weight by decreasing fat deposition and subsequent fasting leptin levels, without changing the overall growth, fasting blood glucose or serum insulin. Gene-targeted deletion of Kv1.3 in MC4R-null mice significantly extended lifespan and increased reproductive success. Basal or light-phase mass-specific metabolic rate and locomotor activity were not affected by genetic deletion of Kv1.3 in MC4R-null mice but dark-phase locomotor activity and mass-specific metabolism were significantly increased resulting in increased total energy expenditure. Conclusions: Gene-targeted deletion of Kv1.3 can reduce adiposity and total body weight in a genetic model of obesity by increasing both locomotor activity and mass-specific metabolism.