Longitudinal data collection of Mycobacterium avium subspecies Paratuberculosis infections in dairy herds: the value of precise field data

Longitudinal infection data on Mycobacterium avium subspecies paratuberculosis (MAP) was collected on three dairy farms in Northeastern United States during approximately 10 years. Precise data on animal characteristics and animal location within farm were collected on these farms. Cows were followed over time with regard to MAP status during biannual fecal and serum sampling and quarterly serum sampling. Approximately 13 000 serum samples, 6500 fecal samples and 2000 tissue samples were collected during these years. Prevalence of positive samples was 1.4% for serological samples, 2.2% in fecal samples and 16.7% in tissue samples. Infection dynamics of MAP was studied and resulted in a number of potential changes in our understanding of MAP infection dynamics. First, a high prevalence of MAP infection was observed in these herds due to lifetime follow up of cows, including slaughter. Second, two distinctly different infection patterns were observed, so called non-progressors and progressors. Non-progressors were characterized by intermittent and low shedding of MAP bacteria and a virtual absence of a humoral immune response. Progressors were characterized by continuous and progressive shedding and a clearly detectable and progressive humoral immune response. Strain typing of MAP isolates on the three farms identified on two of three farms a dominant strain type, indicating that some strains are more successful in terms of transmission and infection progression. Continuous high quality longitudinal data collection turned out to be an essential tool in our understanding of pathobiology and epidemiology of MAP infections in dairy herds.     

Fractionated oral dosing and its effect on cyclophosphamide pharmacokinetics in dogs with high-grade multicentric lymphoma

Cyclophosphamide (CP) is an alkylating agent commonly included in multi-drug treatment protocols for canine cancer. As a prodrug, CP requires hepatic metabolism for activation to the intermediate compound 4-hydroxycyclophosphamide (4-OHCP) which then spontaneously forms alkylating phosphoramide mustard. CP is frequently administered in a fractionated manner, with the total dose given over multiple days. CP is reported to cause auto-induction of metabolism in humans, with faster CP clearance and relatively increased 4-OHCP formation following fractionated versus bolus dosing, however canine pharmacokinetic studies of CP dose fractionation are lacking. The study objective was to evaluate the pharmacokinetics of fractionated oral CP dosing at a dose of 200–250 mg/m² over 3 to 4 days in a prospectively identified population of cancer-bearing dogs. Plasma concentrations of CP and 4-OHCP were measured by ultra-high performance liquid chromatography tandem-mass spectrometry in eight dogs following the first and last doses to assess for auto-induction of CP metabolism. No significant difference in the rate of CP elimination between first and last doses were detected (0.73 ± 0.46 vs. 1.22 ± 0.5 h⁻¹; p = .125). Additionally, no significant difference in dose-normalized 4-OHCP exposure was identified between first and last doses (5.9 ± 2.1 vs. 7.9 ± 6.4 h × ng/ml; p = .936). These results suggest that fractionated dosing may not increase exposure to the active metabolite of CP in dogs as it does in humans. As such, standard bolus dosing and fractionated dosing may be equivalent in terms of bio-activation of CP in dogs administered a dose of 200–250 mg/m².     

Potential long-term growth gains from early clump thinning of coppice-regenerated oak stands

A study was established in the Missouri Ozarks to evaluate coppice regeneration of oak. Five years after a 32-year-old stand was clearcut and regenerated naturally through stump sprouts, the dominant sprout on each stump was identified based upon height. Treated plots were thinned to the single dominant sprout on each stump whereas control plots were not thinned. Twenty-five years later the largest 247, 371, 494, and 618 stems per ha were examined and height of the dominant sprout at age 5 was found to be strongly related to dbh at age 30 in both thinned and unthinned plots. However, in the thinned plots, the largest 494 stems per ha were on average 11%, 28%, and 58% greater, respectively, in height, dbh, and volume compared to similar dominant sprouts in unthinned plots. Logistic regression analysis was used to develop curves for the evaluation of potential gains from clump thinning. In this analysis, the average height of a stand at age 5 was used to estimate thinning gains at age 30.     

Annualized diameter and height growth equations for Pacific Northwest plantation-grown Douglas-fir, western hemlock, and red alder

Simulating the influence of intensive management and annual weather fluctuations on tree growth requires a shorter time step than currently employed by most regional growth models. High-quality data sets are available for several plantation species in the Pacific Northwest region of the United States, but the growth periods ranged from 2 to 12 years in length. Measurement periods of varying length complicate efforts to fit growth models because observed growth rates must be interpolated to a common length growth period or those growth periods longer or shorter than the desired model time step must be discarded. A variation of the iterative technique suggested by Cao [Cao, Q.V., 2000. Prediction of annual diameter growth and survival for individual trees from periodic measurements. Forest Sci. 46, 127–131] was applied to estimate annualized diameter and height growth equations for pure plantations of Douglas-fir, western hemlock, and red alder. Using this technique, fits were significantly improved for all three species by embedding a multi-level nonlinear mixed-effects framework (likelihood ratio test: p < 0.0001). The final models were consistent with expected biological behavior of diameter and height growth over tree, stand, and site variables. The random effects showed some correlation with key physiographic variables such as slope and aspect for Douglas-fir and red alder, but these relationships were not observed for western hemlock. Further, the random effects were more correlated with physiographic variables than actual climate or soils information. Long-term simulations (12–16 years) on an independent dataset using these annualized equations showed that the multi-level mixed effects models were more accurate and precise than those fitted without random effects as mean square error (MSE) was reduced by 13 and 21% for diameter and height growth prediction, respectively. The level of prediction error was also smaller than an existing similar growth model with a longer time step (ORGANON v8) as the annualized equations reduced MSE by 17 and 38% for diameter and height growth prediction, respectively. These models will prove to be quite useful for understanding the interaction of weather and silviculture in the Pacific Northwest and refining the precision of future growth model projections.