Effects of Feeding a Novel Alfalfa Leaf Pellet Product (ProLEAF MAX) and Alfalfa Stems (ProFiber Plus) on Performance in the Feedlot and Carcass Quality of Beef Steers

Alfalfa is often included in the diets of beef animals; however, the nutrient content of alfalfa is variable depending on the region in which it is grown, climate, soil, and many other factors. The leaf portion of alfalfa has a less variable nutrient composition than the stem portion of the plant. The variability that is present in the alfalfa plant can make the development of total mixed rations of consistent nutrient content difficult. As such, the purpose of this study was to determine how the inclusion of fractionated alfalfa leaves and alfalfa stems impacts performance and carcass quality of finishing beef steers. Twenty-four steers were allocated to one of three treatments: a control group fed a typical finishing diet with alfalfa as the forage (CON; n = 8), a typical diet that replaced alfalfa with fractionated alfalfa leaf pellets and alfalfa stems (ProLEAF MAX™ + ProFiber Plus™; PLM+PFP; n = 8), or a typical diet that replaced alfalfa with alfalfa stems (PFP; n = 8) for 63 days. Steers were fed individually once daily, weighed every 14 days and ultrasound images were collected every 28 days. At the end of the feeding trial, steers were harvested at a commercial facility and carcass data was obtained. Analysis of dry matter intake demonstrated that steers receiving the PFP and CON diets consumed more feed (P \u3c 0.001) than steers consuming the PLM+PFP diet. Steers receiving the PLM+PFP diet gained less (P \u3c 0.001) weight than the steers receiving the other two dietary treatments. No differences (P \u3e 0.10) in feed efficiency or carcass characteristics were observed. Steers receiving the PFP diet had improved (P = 0.016) cost of gain ($0.93 per kg) when compared with steers receiving PLM+PFP ($1.08 per kg) diet. Overall, our findings demonstrate that the inclusion of PFP in place of alfalfa hay in a finishing diet has the potential to improve cost of gain, without negatively affecting growth, performance, or carcass characteristics of finishing feedlot steers

The use of discrete choice experiments to inform health workforce policy: a systematic review.

BACKGROUND: Discrete choice experiments have become a popular study design to study the labour market preferences of health workers. Discrete choice experiments in health, however, have been criticised for lagging behind best practice and there are specific methodological considerations for those focused on job choices. We performed a systematic review of the application of discrete choice experiments to inform health workforce policy. METHODS: We searched for discrete choice experiments that examined the labour market preferences of health workers, including doctors, nurses, allied health professionals, mid-level and community health workers. We searched Medline, Embase, Global Health, other databases and grey literature repositories with no limits on date or language and contacted 44 experts. Features of choice task and experimental design, conduct and analysis of included studies were assessed against best practice. An assessment of validity was undertaken for all studies, with a comparison of results from those with low risk of bias and a similar objective and context. RESULTS: Twenty-seven studies were included, with over half set in low- and middle-income countries. There were more studies published in the last four years than the previous ten years. Doctors or medical students were the most studied cadre. Studies frequently pooled results from heterogeneous subgroups or extrapolated these results to the general population. Only one third of studies included an opt-out option, despite all health workers having the option to exit the labour market. Just five studies combined results with cost data to assess the cost effectiveness of various policy options. Comparison of results from similar studies broadly showed the importance of bonus payments and postgraduate training opportunities and the unpopularity of time commitments for the uptake of rural posts. CONCLUSIONS: This is the first systematic review of discrete choice experiments in human resources for health. We identified specific issues relating to this application of which practitioners should be aware to ensure robust results. In particular, there is a need for more defined target populations and increased synthesis with cost data. Research on a wider range of health workers and the generalisability of results would be welcome to better inform policy

Mechanisms of T cell organotropism

F.M.M.-B. is supported by the British Heart Foundation, the Medical Research Council of the UK and the Gates Foundation

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The Impact of Polyamine Precursors, Polyamines, and Steroid Hormones on Temporal Messenger RNA Abundance in Bovine Satellite Cells Induced to Differentiate

Emerging research suggests that hormones found in anabolic implants interact with polyamine biosynthesis. The objective of this study was to determine the effects of steroidal hormones, polyamines and polyamine precursors on bovine satellite cell (BSC) differentiation and polyamine biosynthesis temporally. Primary BSCs were induced to differentiate in 3% horse serum (CON) and treated with 10 nM trenbolone acetate (TBA), 10 nM estradiol (E2), 10 nM TBA and 10 nM E2, 10 mM methionine, 8 mM ornithine, 2 mM putrescine, 1.5 mM spermidine, or 0.5 mM spermine. Total mRNA was isolated 0, 2, 4, 8, 12, 24, and 48 h post-treatment. Abundance of mRNA for genes associated with induction of BSC differentiation: paired box transcription factor 7, myogenic factor 5, and myogenic differentiation factor 1 and genes in the polyamine biosynthesis pathway: ornithine decarboxylase and S-adenosylmethionine—were analyzed. Overall, steroidal hormones did not impact (p &gt; 0.05) mRNA abundance of genes involved in BSC differentiation, but did alter (p = 0.04) abundance of genes involved in polyamine biosynthesis. Polyamine precursors influenced (p &lt; 0.05) mRNA of genes involved in BSC differentiation. These results indicate that polyamine precursors and polyamines impact BSC differentiation and abundance of mRNA involved in polyamine biosynthesis, while steroidal hormones altered the mRNA involved in polyamine biosynthesis