Growth and reproductive performance responses to post-weaning supplementation of early and normally-weaned Brahman crossbred heifers raised in tropical rangelands.

This study investigated the effect of five post-weaning supplementation strategies and two weaning weight groups on long-term growth, puberty and pregnancy percentage of Brahman crossbred heifers. Early-weaned (118 ± 6 kg liveweight) and normally-weaned (183 ± 6 kg liveweight) heifers were allocated to group pens (n = 4 and n = 5/pen for early- and normally-weaned respectively) and offered one of five levels of post-weaning protein supplementation: 0, 1, 2.5, 5 and 10 g of supplement/kg liveweight.day with ad libitum access to a low quality sabi grass (Urochloa mosambicensis) hay during the first dry season (169 days) after weaning. After the post-weaning supplementation period, all heifers grazed the same pastures as a single mob until the end of the experiment and were exposed to fertile bulls from January to May 2016. During the first dry season, supplement intake had a positive linear effect on liveweight gain and hip width gain with no difference in the response between weaning groups. Overall, heifers with higher supplement intakes (i.e. 5 and 10 g/kg) had higher hip height gain (P < 0.005), hip width gain (P < 0.001), body condition score (P < 0.001), and concentration of insulin-like growth factor-1 (P = 0.001), triiodothyronine (P = 0.04) and insulin (P = 0.05) in plasma compared to unsupplemented heifers. These changes resulted in thicker proliferative and hypertrophic zones (both P = 0.03) of the tuber coxae growth plate, larger diameter of terminal hypertrophic chondrocytes (both P = 0.004) at the end of the post-weaning supplementation period when comparing the highest level of supplementation with unsupplemented group. Unsupplemented heifers from both weaning weight groups demonstrated compensatory liveweight gain over the first wet season while evidence of catch-up growth in skeletal dimensions was observed in the second wet season. The main determining factor for pregnancy status of two-year-old Brahman crossbred heifers was pre-mating liveweight (P < 0.001), the pre-mating liveweight was in turn affected by post-weaning supplementation (P = 0.02) or weaning weight group (P < 0.001). This study further demonstrated the positive relationship between premating weight and the occurrence of pregnancy, with an approximate 300 kg pre-mating liveweight required to achieve approximately 80% (67.1-90.3% for a 95% confidence interval) probability of pregnancy in two-year-old Brahman crossbred heifers mated for 4 months.

Functional profiling of live melanoma samples using a novel automated platform.

AIMS: This proof-of-concept study was designed to determine if functional, pharmacodynamic profiles relevant to targeted therapy could be derived from live human melanoma samples using a novel automated platform. METHODS: A series of 13 melanoma cell lines was briefly exposed to a BRAF inhibitor (PLX-4720) on a platform employing automated fluidics for sample processing. Levels of the phosphoprotein p-ERK in the mitogen-activated protein kinase (MAPK) pathway from treated and untreated sample aliquots were determined using a bead-based immunoassay. Comparison of these levels provided a determination of the pharmacodynamic effect of the drug on the MAPK pathway. A similar ex vivo analysis was performed on fine needle aspiration (FNA) biopsy samples from four murine xenograft models of metastatic melanoma, as well as 12 FNA samples from patients with metastatic melanoma. RESULTS: Melanoma cell lines with known sensitivity to BRAF inhibitors displayed marked suppression of the MAPK pathway in this system, while most BRAF inhibitor-resistant cell lines showed intact MAPK pathway activity despite exposure to a BRAF inhibitor (PLX-4720). FNA samples from melanoma xenografts showed comparable ex vivo MAPK activity as their respective cell lines in this system. FNA samples from patients with metastatic melanoma successfully yielded three categories of functional profiles including: MAPK pathway suppression; MAPK pathway reactivation; MAPK pathway stimulation. These profiles correlated with the anticipated MAPK activity, based on the known BRAF mutation status, as well as observed clinical responses to BRAF inhibitor therapy. CONCLUSION: Pharmacodynamic information regarding the ex vivo effect of BRAF inhibitors on the MAPK pathway in live human melanoma samples can be reproducibly determined using a novel automated platform. Such information may be useful in preclinical and clinical drug development, as well as predicting response to targeted therapy in individual patients.

Teaching prioritization skills: a preceptor forum.

The Medical Specialty Preceptor Council of a large tertiary medical center selected prioritization as a theme to address with medical specialty registered nurse preceptors. Activities included exploration of the literature, personal reflection on preceptor experiences, and creation of a project that culminated in a preceptor forum. The forum included interactive poster stations staged for a drop-in session for preceptors. The stations were developed and staffed by Council members using research and ideas from colleagues.