Predicting likelihood of in vivo chemotherapy response in canine lymphoma using ex vivo drug sensitivity and immunophenotyping data in a machine learning model

We report a precision medicine platform that evaluates the probability of chemotherapy drug efficacy for canine lymphoma by combining ex vivo chemosensitivity and immunophenotyping assays with computational modelling. We isolated live cancer cells from fresh fine needle aspirates of affected lymph nodes and collected post‐treatment clinical responses in 261 canine lymphoma patients scheduled to receive at least 1 of 5 common chemotherapy agents (doxorubicin, vincristine, cyclophosphamide, lomustine and rabacfosadine). We used flow cytometry analysis for immunophenotyping and ex vivo chemosensitivity testing. For each drug, 70% of treated patients were randomly selected to train a random forest model to predict the probability of positive Veterinary Cooperative Oncology Group (VCOG) clinical response based on input variables including antigen expression profiles and treatment sensitivity readouts for each patient's cancer cells. The remaining 30% of patients were used to test model performance. Most models showed a test set ROC‐AUC > 0.65, and all models had overall ROC‐AUC > 0.95. Predicted response scores significantly distinguished (P < .001) positive responses from negative responses in B‐cell and T‐cell disease and newly diagnosed and relapsed patients. Patient groups with predicted response scores >50% showed a statistically significant reduction (log‐rank P < .05) in time to complete response when compared to the groups with scores <50%. The computational models developed in this study enabled the conversion of ex vivo cell‐based chemosensitivity assay results into a predicted probability of in vivo therapeutic efficacy, which may help improve treatment outcomes of individual canine lymphoma patients by providing predictive estimates of positive treatment response.     

Decreasing Precipitation Variability Does Not Elicit Major Aboveground Biomass or Plant Diversity Responses in a Mesic Rangeland

Inter- (between years) and intra- (within year) annual variability of precipitation are high on rangelands. We used replicated rainout shelters in a southern tallgrass prairie ecosystem to decrease precipitation variability for 3 yr (1999–2001). We removed interannual variability in total precipitation plus either 1) interannual variability in the seasonal distribution of precipitation (seasonal distribution) or 2) all additional variability in precipitation, including within-year differences in precipitation (even distribution). Our objective was to determine if decreasing variability in precipitation elicits aboveground biomass and plant diversity responses. Aboveground biomass was harvested in June (peak biomass) and December (end of growing season). Plant species diversity, richness, and evenness were determined each June. Reducing precipitation variability had limited effects on total aboveground biomass, grass and forb biomass, and biomass of key species across the 3 yr of investigation. Species richness, species diversity, species evenness, and functional group richness and diversity all were similar across the precipitation treatments across years. Total aboveground biomass and biomass of the dominant C4 perennial grasses little bluestem (Schizachyrium scoparium) and Indiangrass (Sorghastrum nutans) generally were not responsive to the precipitation treatments. However, one species-specific response did occur with the annual forb firewheel (Gaillardia pulchella Foug.) displaying consistent increases in biomass in the seasonal distribution precipitation treatment across all 3 yr. This suggests that increased predictability of precipitation at a given stage of this species’s growth can elicit changes in productivity of a single species that are not manifest at the community level due to constraints of the dominant species. These findings indicate that the southern tallgrass prairie ecosystem is adaptable to changes in precipitation to result in relatively stable production that facilitates simpler predictions in response to altered precipitation regimes.     

Climate Change and North American Rangelands: Trends,Projections, and Implications

The amplified “greenhouse effect” associated with increasing concentrations of greenhouse gases has increased atmospheric temperature by 1°C since industrialization (around 1750), and it is anticipated to cause an additional 2°C increase by mid-century. Increased biospheric warming is also projected to modify the amount and distribution of annual precipitation and increase the occurrence of both drought and heat waves. The ecological consequences of climate change will vary substantially among ecoregions because of regional differences in antecedent environmental conditions; the rate and magnitude of change in the primary climate change drivers, including elevated carbon dioxide (CO₂), warming and precipitation modification; and nonadditive effects among climate drivers. Elevated atmospheric CO₂ will directly stimulate plant growth and reduce negative effects of drying in a warmer climate by increasing plant water use efficiency; however, the CO₂ effect is mediated by environmental conditions, especially soil water availability. Warming and drying are anticipated to reduce soil water availability, net primary productivity, and other ecosystem processes in the southern Great Plains, the Southwest, and northern Mexico, but warmer and generally wetter conditions will likely enhance these processes in the northern Plains and southern Canada. The Northwest will warm considerably, but annual precipitation is projected to change little despite a large decrease in summer precipitation. Reduced winter snowpack and earlier snowmelt will affect hydrology and riparian systems in the Northwest. Specific consequences of climate change will be numerous and varied and include modifications to forage quantity and quality and livestock production systems, soil C content, fire regimes, livestock metabolism, and plant community composition and species distributions, including range contraction and expansion of invasive species. Recent trends and model projections indicate continued directional change and increasing variability in climate that will substantially affect the provision of ecosystem services on North American rangelands.     

Polymorphism of BMPR1B,BMP15 and GDF9 fecundity genes in prolific Garole sheep

Tropical Animal Health and Production - Mutation studies in different prolific sheep breeds have shown that the transforming growth factor beta super family ligands viz. the growth differentiation...     

Inherited c'2 deficiency in man: lack of immunochemically detectable c'2 protein in serums from deficient individuals

Monospecific antiserum to highly purified second component of human complement (C'2) was used to show the absence of the protein from the serums of four persons homozygous for a hereditary deficiency of second-component activity. Serum from an individual heterozygous for the deficiency contained a reduced amount of this protein as compared to the concentration in normal serum. These observations indicate that genetic deficiency of this component is due to failure of synthesis of normal amounts of the protein rather than to synthesis of an antigenically related, hemolytically inactive analog of C'2.     

Human monocytes: distinct receptor sites for the third component of complement and for immunoglobulin G

Human monocytes contain two distinct receptor sites, one specific for the third component of complement (C'3), the other for immunoglobulin G(gammaG). The two receptors may function either independently or cooperatively in the induction of phagocytosis. Ingestion of erythrocytes coated with immunoglobulin M antibody requires a relatively large number of bound C'3 molecules per cell. Ingestion of erythrocytes sensitized with gammaG antibody is independent of complement; however, the reaction is inhibited by concentrations of gammaG far below those in normal serum. Inhibition by gammaG-globulin is overcome by a relatively small number of bound C'3 molecules per cell. The two monocyte receptors exert a cooperative effect on ingestion by monocytes of erythrocytes coated with gammaG antibody in the presence of inhibitory amounts of free gammaG.