Persistent Spillback of Bovine Tuberculosis From White-Tailed Deer to Cattle in Michigan, USA: Status, Strategies, and Needs

Free-ranging white-tailed deer (Odocoileus virginianus) are believed to be a self-sustaining reservoir for bovine tuberculosis (bTB) in northeastern Lower Michigan, USA. Although a comprehensive control program is in place and on-farm mitigation strategies to curtail bTB transmission between cattle and deer have been implemented for over a decade, cattle and deer continue to become infected with the disease. Thus, renewed motivation to eradicate bTB is needed if that is truly the goal. Recurrent detection of bTB in cattle in the region is of mounting concern for state and federal agricultural agencies, producers, and wildlife managers. Current on-farm mitigation efforts include fencing and refined cattle feeding and watering practices. Liberal removal of antlerless deer through hunter harvest and disease control permits (DCPs) issued to cattle producers and agency sharp shooters have also been ongoing. Although these strategies have merit and efforts to reduce prevalence in deer and occurrence of positive farms are elevated, additional actions are needed. Heightened management actions to combat bTB in deer could include deer vaccination programs, strategic habitat manipulations to redistribute deer from farms, and precision removal of deer in proximity to high-risk farms. Foundational research to address development and delivery of vaccine to free-ranging deer is complete. Strategic management and habitat manipulation could reduce and disperse local concentrations of deer while better meeting wildlife, forestry, and agricultural goals. The responses of local deer populations to targeted removal of individuals are generally understood and there is potential to reduce deer activity around agricultural operations while allowing them to persist nearby on natural foods. We summarize the history and progress to date, discuss the realized merit of novel management strategies, and suggest options to rid deer and cattle in Michigan of bTB

Persistent Spillback of Bovine Tuberculosis From White-Tailed Deer to Cattle in Michigan, USA: Status, Strategies, and Needs

Free-ranging white-tailed deer (Odocoileus virginianus) are believed to be a self-sustaining reservoir for bovine tuberculosis (bTB) in northeastern Lower Michigan, USA. Although a comprehensive control program is in place and on-farm mitigation strategies to curtail bTB transmission between cattle and deer have been implemented for over a decade, cattle and deer continue to become infected with the disease. Thus, renewed motivation to eradicate bTB is needed if that is truly the goal. Recurrent detection of bTB in cattle in the region is of mounting concern for state and federal agricultural agencies, producers, and wildlife managers. Current on-farm mitigation efforts include fencing and refined cattle feeding and watering practices. Liberal removal of antlerless deer through hunter harvest and disease control permits (DCPs) issued to cattle producers and agency sharp shooters have also been ongoing. Although these strategies have merit and efforts to reduce prevalence in deer and occurrence of positive farms are elevated, additional actions are needed. Heightened management actions to combat bTB in deer could include deer vaccination programs, strategic habitat manipulations to redistribute deer from farms, and precision removal of deer in proximity to high-risk farms. Foundational research to address development and delivery of vaccine to free-ranging deer is complete. Strategic management and habitat manipulation could reduce and disperse local concentrations of deer while better meeting wildlife, forestry, and agricultural goals. The responses of local deer populations to targeted removal of individuals are generally understood and there is potential to reduce deer activity around agricultural operations while allowing them to persist nearby on natural foods. We summarize the history and progress to date, discuss the realized merit of novel management strategies, and suggest options to rid deer and cattle in Michigan of bTB

Use of rhodamine B as a biomarker in a simulated oral vaccine deployment against bovine tuberculosis in white-tailed deer

IntroductionFree-ranging white-tailed deer (Odocoileus virginianus) in northeastern lower Michigan, (United States) are a self-sustaining reservoir for bovine tuberculosis (bTB). Farm mitigation practices, baiting bans, and antlerless deer harvests have been ineffective in eliminating bTB in white-tailed deer and risks to cattle. The apparent prevalence has remained relatively constant in deer, prompting interest among wildlife researchers, managers, and veterinarians for an effective means of vaccinating deer against bTB. The commonly used human vaccine for bTB, Bacillus Calmette Guerin (BCG), is the primary candidate with oral delivery being the logical means for vaccinating deer.Materials and methodsWe developed vaccine delivery units and incorporated the biomarker Rhodamine B before delivering them to deer to assess the level of coverage achievable. Following deployment of Rhodamine B-laden vaccine delivery units on 17 agricultural study sites in Alpena County, MI in Mar/Apr 2016, we sampled deer to detect evidence of Rhodamine B consumption.Results and discussionWe collected a total of 116 deer and sampled them for vibrissae/rumen marking and found 66.3% (n = 77) of the deer collected exhibited evidence of vaccine delivery unit consumption. Understanding the level of coverage we achieved with oral delivery of a biomarker in vaccine delivery units to deer enables natural resource professionals to forecast expectations of a next step toward further minimizing bTB in deer

Whole Exome Sequencing of Cell-Free DNA for Early Lung Cancer: A Pilot Study to Differentiate Benign From Malignant CT-Detected Pulmonary Lesions

Introduction: Indeterminate pulmonary lesions (IPL) detected by CT pose a significant clinical challenge, frequently necessitating long-term surveillance or biopsy for diagnosis. In this pilot investigation, we performed whole exome sequencing (WES) of plasma cell free (cfDNA) and matched germline DNA in patients with CT-detected pulmonary lesions to determine the feasibility of somatic cfDNA mutations to differentiate benign from malignant pulmonary nodules.Methods: 33 patients with a CT-detected pulmonary lesions were retrospectively enrolled (n = 16 with a benign nodule, n = 17 with a malignant nodule). Following isolation and amplification of plasma cfDNA and matched peripheral blood mononuclear cells (PBMC) from patient blood samples, WES of cfDNA and PBMC DNA was performed. After genomic alignment and filtering, we looked for lung-cancer associated driver mutations and next identified high-confidence somatic variants in both groups.Results: Somatic cfDNA mutations were observed in both groups, with the cancer group demonstrating more variants than the benign group (1083 ± 476 versus 553 ± 519, p < 0.0046). By selecting variants present in >2 cancer patients and not the benign group, we accurately identified 82% (14/17) of cancer patients.Conclusions: This study suggests a potential role for cfDNA for the early identification of lung cancer in patients with CT-detected pulmonary lesions. Importantly, a substantial number of somatic variants in healthy patients with benign pulmonary nodules were also found. Such “benign” variants, while largely unexplored to date, have widespread relevance to all liquid biopsies if cfDNA is to be used accurately for cancer detection

A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer

ATP Binding Cassette B1 (ABCB1) is a transporter with a broad substrate specificity involved in the elimination of several carcinogens from the gut. Several polymorphic variants within the ABCB1 gene have been reported as modulators of ABCB1-mediated transport. We investigated the impact of ABCB1 genetic variants on colorectal cancer (CRC) risk. A hybrid tagging/functional approach was performed to select 28 single nucleotide polymorphisms (SNPs) that were genotyped in 1,321 Czech subjects, 699 CRC cases and 622 controls. In addition, six potentially functional SNPs were genotyped in 3,662 German subjects, 1,809 cases and 1,853 controls from the DACHS study. We found that three functional SNPs (rs1202168, rs1045642 and rs868755) were associated with CRC risk in the German population. Carriers of the rs1202168_T and rs868755_T alleles had an increased risk for CRC (Ptrend = 0.016 and 0.029, respectively), while individuals bearing the rs1045642_C allele showed a decreased risk of CRC (Ptrend = 0.022). We sought to replicate the most significant results in an independent case-control study of 3,803 subjects, 2,169 cases and 1,634 controls carried out in the North of Germany. None of the SNPs tested were significantly associated with CRC risk in the replication study. In conclusion, in this study of about 8,800 individuals we show that ABCB1 gene polymorphisms play at best a minor role in the susceptibility to CRC

Identification of Potential Prognostic Biomarkers in Patients with Untreated, Advanced Pancreatic Cancer from a Phase III Trial (CALGB 80303)

Patients with advanced stage adenocarcinoma of the pancreas have a poor prognosis. The identification of prognostic and/or predictive biomarkers may help stratify patients so that therapy can be individualized

Climatic and geographic predictors of life history variation in Eastern Massasauga (Sistrurus catenatus): A range-wide synthesis

Elucidating how life history traits vary geographically is important to understanding variation in population dynamics. Because many aspects of ectotherm life history are climate-dependent, geographic variation in climate is expected to have a large impact on population dynamics through effects on annual survival, body size, growth rate, age at first reproduction, size-fecundity relationship, and reproductive frequency. The Eastern Massasauga (Sistrurus catenatus) is a small, imperiled North American rattlesnake with a distribution centered on the Great Lakes region, where lake effects strongly influence local conditions. To address Eastern Massasauga life history data gaps, we compiled data from 47 study sites representing 38 counties across the range. We used multimodel inference and general linear models with geographic coordinates and annual climate normals as explanatory variables to clarify patterns of variation in life history traits. We found strong evidence for geographic variation in six of nine life history variables. Adult female snout-vent length and neonate mass increased with increasing mean annual precipitation. Litter size decreased with increasing mean temperature, and the size-fecundity relationship and growth prior to first hibernation both increased with increasing latitude. The proportion of gravid females also increased with increasing latitude, but this relationship may be the result of geographically varying detection bias. Our results provide insights into ectotherm life history variation and fill critical data gaps, which will inform Eastern Massasauga conservation efforts by improving biological realism for models of population viability and climate change

Characterizing Associations and SNP-Environment Interactions for GWAS-Identified Prostate Cancer Risk Markers—Results from BPC3

Genome-wide association studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. However, whether these associations can be consistently replicated, vary with disease aggressiveness (tumor stage and grade) and/or interact with non-genetic potential risk factors or other SNPs is unknown. We therefore genotyped 39 SNPs from regions identified by several prostate cancer GWAS in 10,501 prostate cancer cases and 10,831 controls from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We replicated 36 out of 39 SNPs (P-values ranging from 0.01 to 10−28). Two SNPs located near KLK3 associated with PSA levels showed differential association with Gleason grade (rs2735839, P = 0.0001 and rs266849, P = 0.0004; case-only test), where the alleles associated with decreasing PSA levels were inversely associated with low-grade (as defined by Gleason grade <8) tumors but positively associated with high-grade tumors. No other SNP showed differential associations according to disease stage or grade. We observed no effect modification by SNP for association with age at diagnosis, family history of prostate cancer, diabetes, BMI, height, smoking or alcohol intake. Moreover, we found no evidence of pair-wise SNP-SNP interactions. While these SNPs represent new independent risk factors for prostate cancer, we saw little evidence for effect modification by other SNPs or by the environmental factors examined

Identification of an autoantibody panel to separate lung cancer from smokers and nonsmokers

<p>Abstract</p> <p>Background</p> <p>Sera from lung cancer patients contain autoantibodies that react with tumor associated antigens (TAAs) that reflect genetic over-expression, mutation, or other anomalies of cell cycle, growth, signaling, and metabolism pathways.</p> <p>Methods</p> <p>We performed immunoassays to detect autoantibodies to ten tumor associated antigens (TAAs) selected on the basis of previous studies showing that they had preferential specificity for certain cancers. Sera examined were from lung cancer patients (22); smokers with ground-glass opacities (GGOs) (46), benign solid nodules (55), or normal CTs (35); and normal non-smokers (36). Logistic regression models based on the antibody biomarker levels among the high risk and lung cancer groups were developed to identify the combinations of biomarkers that predict lung cancer in these cohorts.</p> <p>Results</p> <p>Statistically significant differences in the distributions of each of the biomarkers were identified among all five groups. Using Receiver Operating Characteristic (ROC) curves based on age, c-myc, Cyclin A, Cyclin B1, Cyclin D1, CDK2, and survivin, we obtained a sensitivity = 81% and specificity = 97% for the classification of cancer vs smokers(no nodules, solid nodules, or GGO) and correctly predicted 31/36 healthy controls as noncancer.</p> <p>Conclusion</p> <p>A pattern of autoantibody reactivity to TAAs may distinguish patients with lung cancer versus smokers with normal CTs, stable solid nodules, ground glass opacities, or normal healthy never smokers.</p