Sheep fatigue during transport: Lost in translation?

Although sheep are commonly transported long distances, and sheep welfare during transport is a topic of research and policy discussion, the subject of their fatigue during transport has been under-researched. The current qualitative study, focused on the EU and UK, aimed to critically analyse stakeholder views on issues relating to sheep fatigue, including behavioural indications of fatigue, the interplay between fatigue and other factors, and the practicalities of identifying fatigue in commercial transport conditions. Insight into stakeholder perceptions of these issues could contribute to the body of knowledge regarding sheep fatigue during transport, potentially playing a part in future efforts to improve fatigue understanding and detection.

Prediction of the Renal Organic Anion Transporter 1 (OAT1)- Mediated Drug Interactions for LY404039, the Active Metabolite of Pomaglumetad Methionil.

Purpose: The objective of this work was to demonstrate that clinical OAT1-mediated DDIs can be predicted using physiologically based pharmacokinetic (PBPK) modeling.

Methods: LY404039 is a metabotropic glutamate receptor 2/3 agonist and the active moiety of the prodrug pomaglumetad methionil (LY2140023). After oral administration, pomaglumetad methionil is rapidly taken up by enterocytes via PEPT1 and once absorbed, converted to LY404039 via membrane dehydropeptidase 1 (DPEP1).

Welfare of domestic birds and rabbits transported in containers.

This opinion, produced upon a request from the European Commission, focuses on transport of domestic birds and rabbits in containers (e.g. any crate, box, receptacle or other rigid structure used for the transport of animals, but not the means of transport itself).

Long-Distance Transport of Finisher Pigs in the Iberian Peninsula: Effects of Season on Thermal and Enthalpy Conditions, Welfare Indicators and Meat pH.

Current legislation in the European Union places limits on live pig transport according to outside temperature, but less is known about the effects of sudden changes in the thermal microenvironment in trailers, particularly during long-distance transport. In this study, we measured the temperature and relative humidity inside livestock vehicles carrying 1920 Spanish finisher pigs (live weight 100 kg and 240 animals per journey) during eight long-distance (>15 h) commercial journeys to slaughter from northern Spain to Portugal in the summer and winter. Here, we report the rate of change in the air temperature (°C × min) and air enthalpies in the transport vehicle (kg water kg dry air-1).

DIAGNOSING AND CATEGORIZING LEPROSY IN LIVE EURASIAN RED SQUIRRELS () FOR MANAGEMENT, SURVEILLANCE, AND TRANSLOCATION PURPOSES.

The presence of and in Eurasian red squirrel (, ERS) carcasses throughout the British Isles, and leprosy as a disease, have recently been reported using histological and molecular diagnostic methods. In 2016, the first longitudinal study of ERS affected by leprosy was initiated. One of the main challenges was the reliable diagnosis of leprosy in live ERS, which is important for (a) welfare and case management and (b) surveillance or pretranslocation screening efforts.

Impact of pre-slaughter factors on welfare of broilers.

Pre-slaughter factors adversely affecting bird welfare were studied at the slaughterhouse. The incidence of dead on arrival (DoA), bruises and dehydration was investigated in 64 different mixed-sex batches of broilers coming from 64 different farms rearing fast-growing genotypes (Ross or Cobb). The effects of catching team, method of catching, time of day for catching and transport, density per cage, transport duration, transport distance, lairage duration and water withdrawal were considered.

Spectral entropy of early-life distress calls as an iceberg indicator of chicken welfare.

Chicks () make a repetitive, high energy 'distress' call when stressed. Distress calls are a catch-all response to a range of environmental stressors, and elicit food calling and brooding from hens. Pharmacological and behavioural laboratory studies link expression of this call with negative affective state.

Evaluation of reticuloruminal pH measurements from individual cattle: Sampling strategies for the assessment of herd status.

The application of pH observations to clinical practice in dairy cattle is based on criteria derived primarily from single time-point observations more than 20 years ago. The aims of this study were to evaluate these criteria using data collected using continuous recording methods; to make recommendations that might improve their interpretation; and to determine the relationship between the number of devices deployed in a herd and the accuracy of the resulting estimate of the herd-mean reticuloruminal pH. The study made use of 815,475 observations of reticuloruminal pH values obtained from 75 cattle in three herds (one beef and two twice-daily milking herds) to assess sampling strategies for the diagnosis of sub-acute rumen acidosis (SARA), and to evaluate the ability of different numbers of bolus devices to accurately estimate the true herd-mean reticuloruminal pH value at any time.

First Evaluation of Infrared Thermography as a Tool for the Monitoring of Udder Health Status in Farms of Dairy Cows.

The aim of the present study was to test infrared thermography (IRT), under field conditions, as a possible tool for the evaluation of cow udder health status. Thermographic images (n. 310) from different farms (n.

Development of a Machine Vision Method for the Monitoring of Laying Hens and Detection of Multiple Nest Occupations.

Free range systems can improve the welfare of laying hens. However, the access to environmental resources can be partially limited by social interactions, feeding of hens, and productivity, can be not stable and damaging behaviors, or negative events, can be observed more frequently than in conventional housing systems. In order to reach a real improvement of the hens' welfare the study of their laying performances and behaviors is necessary.

Relative bioavailability of three formulations of galunisertib administered as monotherapy in patients with advanced or metastatic cancer.

Objective: Galunisertib (LY2157299 monohydrate), an inhibitor of the transforming growth factor β (TGFβ) pathway, is currently under investigation in several clinical trials involving multiple tumor types. The primary objective of this study was to assess relative bioavailability of two new galunisertib formulations developed using the roller compaction (RC) dry-milled (RCD) and RC slurry-milled (RCS) processes, compared with the existing formulation developed using the high-sheer wet granulation (HSWG) process. The secondary objective was to report the safety profile after a single dose of the three formulations.

In Vitro and Clinical Evaluations of the Drug-Drug Interaction Potential of a Metabotropic Glutamate 2/3 Receptor Agonist Prodrug with Intestinal Peptide Transporter 1.

Despite peptide transporter 1 (PEPT1) being responsible for the bioavailability for a variety of drugs, there has been little study of its potential involvement in drug-drug interactions. Pomaglumetad methionil, a metabotropic glutamate 2/3 receptor agonist prodrug, utilizes PEPT1 to enhance absorption and bioavailability. In vitro studies were conducted to guide the decision to conduct a clinical drug interaction study and to inform the clinical study design.

Evaluation of the effect of necitumumab on the corrected QT interval in patients with advanced solid tumors.

Purpose: Necitumumab is a second-generation, recombinant, human immunoglobulin G1 monoclonal antibody that blocks the ligand binding site of the epidermal growth factor receptor. The primary objective of this phase 2 study, conducted in accordance with International Conference on Harmonisation E14 guidance, was to determine the effect of necitumumab treatment on QT/QTc interval in patients with advanced solid tumors.

Methods: Patients received necitumumab monotherapy at an absolute dose of 800 mg, once per week for each 6-week cycle.

Behavioural, brain and cardiac responses to hypobaric hypoxia in broiler chickens.

A novel approach to pre-slaughter stunning of chickens has been developed in which birds are rendered unconscious by progressive hypobaric hypoxia. Termed Low Atmospheric Pressure Stunning (LAPS), this approach involves application of gradual decompression lasting 280s according to a prescribed curve. We examined responses to LAPS by recording behaviour, electroencephalogram (EEG) and electrocardiogram (ECG) in individual male chickens, and interpreted these with regard to the welfare impact of the process.

Amount of Testosterone on Laundered Clothing After Use of Testosterone Topical 2% Solution by Healthy Male Volunteers.

Introduction: Testosterone 2% solution (Axiron) applied to armpit(s) is used for replacement therapy in men with a deficiency of endogenous testosterone.

Aim: To determine the amount of testosterone on subjects' T-shirts 12 hours after applying testosterone solution, the residual testosterone on subjects' T-shirts after laundering, and the testosterone transferred to unworn textile items during laundering with worn T-shirts.

Methods: Healthy males ≥18 years old applied 2 × 1.

Considerations for assessing the potential effects of antidiabetes drugs on cardiac ventricular repolarization: A report from the Cardiac Safety Research Consortium.

Thorough QT studies conducted according to the International Council on Harmonisation E14 guideline are required for new nonantiarrhythmic drugs to assess the potential to prolong ventricular repolarization. Special considerations may be needed for conducting such studies with antidiabetes drugs as changes in blood glucose and other physiologic parameters affected by antidiabetes drugs may prolong the QT interval and thus confound QT/corrected QT assessments. This review discusses potential mechanisms for QT/corrected QT interval prolongation with antidiabetes drugs and offers practical considerations for assessing antidiabetes drugs in thorough QT studies.

Effect of pomaglumetad methionil on the QT interval in subjects with schizophrenia.

Objective: This thorough QT/QTc (TQT) study assessed the effects of a supratherapeutic dose of pomaglumetad methionil, a potential treatment for schizophrenia, compared to placebo on the QT interval in subjects with schizophrenia.

Methods: This double-blind, 3-period crossover study enrolled 86 subjects aged 22 - 63 years, who met Diagnostic and Statistical Manual, Fourth Edition, Test Revision (DSM-IV-TR) criteria for schizophrenia; 78 subjects completed the study. Subjects were randomly assigned to sequences of 3 treatment periods of single oral doses of pomaglumetad methionil 400 mg, moxifloxacin 400 mg, and placebo.

Relative contributions of presystemic and systemic peptidases to oral exposure of a novel metabotropic glutamate 2/3 receptor agonist (LY404039) after oral administration of prodrug pomaglumetad methionil (LY2140023).

Pomaglumetad methionil (LY2140023) is the prodrug of a novel metabotropic glutamate 2/3 receptor agonist (LY404039) being investigated for the treatment of schizophrenia. Using accelerator mass spectrometry (AMS) and an intravenous (i.v.

Evaluation of the likelihood of a selective CHK1 inhibitor (LY2603618) to inhibit CYP2D6 with desipramine as a probe substrate in cancer patients.

LY2603618 is a selective inhibitor of deoxyribonucleic acid damage checkpoint kinase 1 (CHK1) and has been in development for the enhancement of chemotherapeutic agents. The study described was to assess the potential interaction between LY2603618 and cytochrome P450 isoform 2D6 (CYP2D6) substrate desipramine in patients with cancer. Before clinical investigation, in silico simulations (using Simcyp®) were conducted.

Effect of deodorant and antiperspirant use and presence or absence of axillary hair on absorption of testosterone 2% solution applied to men's axillae.

Introduction: Testosterone 2% solution is applied to axillae and is indicated for testosterone replacement therapy in males deficient in endogenous testosterone.

Aim: This open-label crossover study evaluated the effect of deodorant/antiperspirant use and presence or absence of axillary hair on absorption of testosterone solution.

Methods: Healthy males (N = 30; ≥50 years of age with baseline testosterone <400 ng/dL) were randomized to one of four treatment sequences involving six treatments.

Modeling and simulations to confirm a controlled hypoglycemic stress test in healthy subjects is not associated with clinically significant QT prolongations.

Objectives: A modified insulin tolerance test (ITT) can be used to simulate a physiological stress state through the induction of controlled hypoglycemia in healthy volunteers. This allows for evaluation of hypothalamic-pituitary-adrenocortical axis response to stress via a surge in cortical release. However, a consequence of severe, prolonged hypoglycemia is QT interval prolongation.

Disposition and metabolism of LY2603618, a Chk-1 inhibitor following intravenous administration in patients with advanced and/or metastatic solid tumors.

The disposition and metabolism of a Chk-1 inhibitor (LY2603618) was characterized following a 1-h intravenous administration of a single 250-mg dose of [14C]LY2603618 (50 µCi) to patients with advanced or metastatic solid tumors. LY2603618 was well tolerated with no clinically significant adverse events. Study was limited to three patients due to challenges of conducting ADME studies in patients with advanced cancer.

Effects of duloxetine on norepinephrine and serotonin transporter activity in healthy subjects.

Duloxetine selectively inhibits the serotonin (5-HT) and norepinephrine (NE) transporters (5-HTT and NET, respectively), as demonstrated in vitro and in preclinical studies; however, transporter inhibition has not been fully assessed in vivo at the approved dose of 60 mg/d. Here, the in vivo effects of dosing with duloxetine 60 mg once daily for 11 days in healthy subjects were assessed in 2 studies: (1) centrally (n = 11), by measuring concentrations of 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylglycol (DHPG), and NE in cerebrospinal fluid, and (2) versus escitalopram 20 mg/d (n = 32) in a 2-period crossover study by assessing the ΔDHPG/ΔNE ratio in plasma during orthostatic testing and by pharmacokinetic/pharmacodynamic modeling of reuptake inhibition using subjects' serum in cell lines expressing cloned human 5-HTT or NET. At steady state, duloxetine significantly reduced concentrations of DHPG and 5-hydroxyindoleacetic acid (P < 0.

Single- and multiple-dose pharmacokinetic, safety, and tolerability profiles of olanzapine long-acting injection: an open-label, multicenter, nonrandomized study in patients with schizophrenia.

Background: This was the first study, to our knowledge, in patients with schizophrenia in which olanzapine long-acting injection (LAI) was used to attempt delivery of depot formulation in multiple therapeutic doses.

Objective: This study assessed the safety profile, tolerability, and pharmacokinetic (PK) properties of olanzapine after single and multiple administrations of olanzapine LAI and evaluated maintenance of symptom control.

Methods: This was an open-label, multicenter, nonrandomized study of olanzapine LAI in patients with schizophrenia stabilized with oral olanzapine.