Appearance of choline metabolites in plasma and milk when choline is infused into the abomasum with or without methionine

Four lactating, ruminally cannulated Jersey cows, (mean ± standard deviation) 264 ± 54.2 d in milk and 484 ± 24.1 kg of body weight, were arranged in a 4 × 4 Latin square design to measure the effects of abomasal infusion of choline chloride with or without dl-Met on milk and plasma choline metabolites and plasma AA in cows fed a Met-deficient diet. Cows were randomly assigned to 1 of 4 experimental treatments: (1) control; no supplemental Met or choline (CON), (2) 13 g/d of choline ion delivered via abomasal infusion (CHO), (3) 13 g/d of Met delivered via abomasal infusion (MET), and (4) 13 g/d of choline and 13 g/d of Met delivered via abomasal infusion (CHO + MET). Cows received the same basal diet throughout the experiment, which was formulated to be deficient in Met (−5.0 g of Met using the NASEM, 2021, model). Periods were 7 d in length with d 1 to 2 serving as a wash-out period and cows being infused on d 3 to 7. Milk samples were collected twice daily on d 5 to 7 and were analyzed for fat, true protein, lactose, and choline metabolites including betaine, phosphocholine, and free choline using hydrophilic interaction liquid chromatography-tandem mass spectrometry. Blood samples were collected via venipuncture of the coccygeal vein at 1100, 1300, and 1500 h on d 7 of each period and were analyzed for free AA as well as choline metabolites. Plasma Met increased in response to Met infusion and an interaction with choline and Met infusion was observed in the plasma concentration of branched-chain AA. Cows receiving choline exhibited the greatest Cho yield in milk. Milk phosphocholine yield tended to be highest when both choline and Met were infused

Observations of temporal changes of tritium-3He age in the eastern North Atlantic thermocline: Evidence for changes in ventilation

A compilation of fifteen years of tritium and 3He measurements is used to examine the ventilation of the eastern North Atlantic subtropical gyre with specific emphasis on the temporal character of the tracer age field. A multivariate regression analysis in the form of a spatiotemporal Taylor expansion is applied to observations interpolated onto isopycnal surfaces. The time-dependent component of the tracer age field is found to be statistically significant, explaining approximately 10% of the variance of the tracer age observations in the upper thermocline (σ = 26.5) and increasing to roughly 50% of the variance in the lower thermocline (σ = 27.0). The observed transient tracer age increases over the 15 years of observations with the fractional rate of change of the age field varying between 2% and 5% per year. The largest observed changes occur on the deepest, most slowly ventilated isopycnal surfaces. The second derivative of the tritium-3He age with time suggests that the tracer age field may be approaching a steady state. If tritium-3He age is interpreted as a true measure of the advective ventilation age, the temporal changes in age would imply a slackening of the ventilation of the lower main thermocline of greater than 50% from the late 1970\u27s to the early 1990\u27s. However, consideration of the full advective-diffusive balance of tritium-3He age reveals that the changes in tracer age field represent a time-dependent adjustment of the transient tracer concentrations in conjunction with a steady local circulation field. Integral approximations of the upstream evolution of the tracer field also fail to demonstrate evidence for decadal changes in ventilation. The integral balance along the path of subduction yields an improved estimate of the true ventilation age based on the temporal tendency of the age field along the path of ventilation. An approximation of this integral suggests that actual ventilation ages can be up to 40% larger than the measured tracer age in the deeper portions of the North Atlantic thermocline. Proper accounting of the time-dependent biases of the tracer age dating technique are a prerequisite for examining transient tracer measurements for evidence of changes in the physical ventilation of the upper ocean

Metformin, lipids and atherosclerosis prevention

Purpose of review: We provide an overview of recent publications that extend clinically relevant knowledge relating to metformin's effects on lipids and atherosclerotic vascular disease and/or provide insights into the drug's mechanisms of action on the heart and vasculature. Recent findings: We focus on original research in humans or in human tissues. Several recently completed randomized clinical trials have reported effects of metformin on surrogate measures of atherosclerotic vascular disease, including carotid–intima media thickness, vascular reactivity and calcification in people with Type 1 (T1D) and Type 2 (T2D) diabetes as well as nondiabetic dysglycaemia. In addition, observational studies have provided novel insights into the mechanisms of metformin's effects on carotid plaque, monocytes/macrophages, vascular smooth muscle and endothelial cells, including via 5’-adenosine monophosphate-activated protein kinase (AMPK) activation. Summary: Recent trials based on surrogate outcome measures have provided further data suggesting protective effects of metformin against vascular disease in youth and adults with Type 1 diabetes, as well as in adults with prediabetes and Type 2 diabetes. In parallel, human tissue and cell studies have provided new insights into pleiotropic effects of metformin and suggest novel drug targets. As metformin is an inexpensive agent with an established safety profile, larger scale clinical trials based on hard clinical outcomes [cardiovascular disease (CVD) events] are now indicated

Cost comparison of orthopaedic fracture pathways using discrete event simulation in a Glasgow hospital

Objective: Healthcare faces the continual challenge of improving outcome whilst aiming to reduce cost. The aim of this study was to determine the micro cost differences of the Glasgow non-operative trauma virtual pathway in comparison to a traditional pathway. Design:  Discrete event simulation was used to model and analyse cost and resource utilisation with an activity based costing approach. Data for a full comparison before the process change was unavailable so we utilised a modelling approach, comparing a Virtual Fracture Clinic (VFC) to a simulated Traditional Fracture Clinic (TFC). Setting:  The orthopaedic unit VFC pathway pioneered at Glasgow Royal Infirmary has attracted significant attention and interest and is the focus of this cost study. Outcome measures: Our study focused exclusively on non-operative trauma patients attending Emergency Department or the minor injuries unit and the subsequent step in the patient pathway. Retrospective studies of patient outcomes as a result of the protocol introductions for specific injuries in association with activity costs from the models.ResultsPatients are satisfied with the new pathway, the information provided and the outcome of their injuries (Evidence Level IV). There was a 65% reduction in the number of first outpatient face-to-face attendances in orthopaedics. In the VFC pathway, the resources required per day were significantly lower for all staff groups (p=<0.001). The overall cost per patient of the VFC pathway was £22.84 (95% CI: 21.74, 23.92) per patient compared with £36.81 (95% CI: 35.65, 37.97) for the TFC pathway.  Conclusions:  Our results give a clearer picture of the cost comparison of the virtual pathway over a wholly traditional face-to-face clinic system. The use of simulation-based stochastic costings in healthcare economic analysis has been limited to date, but this study provides evidence for adoption of this method as a basis for its application in other healthcare settings

Redundance of Δ\Delta-isobar Parameters in Effective Field Theories

It is shown that the off-shell parameters in the interaction Lagrangian of pions, nucleons, and $\Delta$-isobars are redundant in the framework of effective field theories. Our results also suggest the necessity of including the $\Delta$ as an explicit dynamical degree of freedom.Comment: 11 pages, RevTex, no figures, a minor error corrected, to appear in PL

Understanding of prognosis in non-metastatic prostate cancer: a randomised comparative study of clinician estimates measured against the PREDICT prostate prognostic model

Abstract: PREDICT Prostate is an individualised prognostic model that provides long-term survival estimates for men diagnosed with non-metastatic prostate cancer (www.prostate.predict.nhs.uk). In this study clinician estimates of survival were compared against model predictions and its potential value as a clinical tool was assessed. Prostate cancer (PCa) specialists were invited to participate in the study. 190 clinicians (63% urologists, 17% oncologists, 20% other) were randomised into two groups and shown 12 clinical vignettes through an online portal. Each group viewed opposing vignettes with clinical information alone, or alongside PREDICT Prostate estimates. 15-year clinician survival estimates were compared against model predictions and reported treatment recommendations with and without seeing PREDICT estimates were compared. 155 respondents (81.6%) reported counselling new PCa patients at least weekly. Clinician estimates of PCa-specific mortality exceeded PREDICT estimates in 10/12 vignettes. Their estimates for treatment survival benefit at 15 years were over-optimistic in every vignette, with mean clinician estimates more than 5-fold higher than PREDICT Prostate estimates. Concomitantly seeing PREDICT Prostate estimates led to significantly lower reported likelihoods of recommending radical treatment in 7/12 (58%) vignettes, particularly in older patients. These data suggest clinicians overestimate cancer-related mortality and radical treatment benefit. Using an individualised prognostic tool may help reduce overtreatment