Understanding the effect of producers' attitudes, perceived norms, and perceived behavioral control on intentions to use antimicrobials prudently on New York dairy farms.

Understanding farmers' behavior, motivations, and perceptions toward antimicrobial use can influence how veterinarians translate research into practice and guide effective ways of implementing protocols. A multidisciplinary team investigated behavioral tendencies of New York dairy farmers toward antimicrobial use by administering a survey modeled with the reasoned action approach. This approach is a framework from social psychology containing the constructs attitude, perceived norms, and perceived behavioral control, and is used in combination with structural equation modeling to determine what drives intentions. Multiple indicators and multiple causes (MIMIC) models were then used to determine the effects of beliefs on their underlying constructs. The objective of the study was to provide direct and indirect measures of the constructs using survey data to determine importance of and associations with intention to use antimicrobials prudently. The structural equation model indicated that perceived behavioral control explained intention. Thus, farmers who feel capable of prudent use expressed positive intentions. Attitude and perception of others also had influence to a lesser extent. MIMIC models showed that the most important attributes of instrumental attitude were increasing profitability, decreasing risk of residues, and increasing herd health. Contributing attributes of affective attitude were job satisfaction, decreasing resistance, and increasing milk production. For perceived norms, the attributes were opinions/approval of family and peers, veterinarians, and milk processors. Finally, for perceived behavioral control, attributes focused on saving money on labor and treatment, ability to fit into the daily routine, and effectiveness with veterinary guidance. In conclusion, the best approach for adoption of practices might be presentation of examples of successful strategies by other producers, particularly in peer groups. In addition, veterinarians should provide the tools and guidance needed to produce economic gain, reduction of risks associated with residues and resistance, and positive experiences when using the tactics.

Suppression of AKT phosphorylation restores rapamycin-based synthetic lethality in SMAD4-defective pancreatic cancer cells.

mTOR has been implicated in survival signals for many human cancers. Rapamycin and TGF-ß synergistically induce G1 cell-cycle arrest in several cell lines with intact TGF-ß signaling pathway, which protects cells from the apoptotic effects of rapamycin during S-phase of the cell cycle. Thus, rapamycin is cytostatic in the presence of serum/TGF-ß and cytotoxic in the absence of serum. However, if TGF-ß signaling is defective, rapamycin induced apoptosis in both the presence and absence of serum/TGF-ß in colon and breast cancer cell lines. Because genetic dysregulation of TGF-ß signaling is commonly observed in pancreatic cancers-with defects in the Smad4 gene being most prevalent, we hypothesized that pancreatic cancers would display a synthetic lethality to rapamycin in the presence of serum/TGF-ß. We report here that Smad4-deficient pancreatic cancer cells are killed by rapamycin in the absence of serum; however, in the presence of serum, we did not observe the predicted synthetic lethality with rapamycin. Rapamycin also induced elevated phosphorylation of the survival kinase Akt at Ser473. Suppression of rapamycin-induced Akt phosphorylation restored rapamycin sensitivity in Smad4-null, but not Smad4 wild-type pancreatic cancer cells. This study shows that the synthetic lethality to rapamycin in pancreatic cancers with defective TGF-ß signaling is masked by rapamycin-induced increases in Akt phosphorylation. The implication is that a combination of approaches that suppress both Akt phosphorylation and mTOR could be effective in targeting pancreatic cancers with defective TGF-ß signaling.