Farm Animal Welfare and Human Health

The paper examines the relationship between farm animal welfare, industrial farm animal production, and human health consequences. The data suggest that when the animal welfare of land-based farm animals is compromised, there are resulting significant negative human health consequences due to environmental degradation, the use of non-therapeutic levels of antibiotics for growth promotion, and the consequences of intensification. This paper accepts that even if meat and fish consumption is reduced, meat and fish will be part of the diet of the future. Industrial production modified from the current intensified systems will still be required to feed the world in 2050 and beyond. This paper identifies the concept of sustainable intensification and suggests that if farm animal welfare is improved, many of the human health consequences of intensified industrial production can be eliminated or reduced. In water-based farm animal production, many new systems are resulting in a product that actually protects the environment and can be done at industrial levels without the use of antibiotics

Conceptual Approaches to Alternate Methods in Toxicological Testing

Due to public pressure, in vivo methods of toxicity testing is being attempted to be replaced by in vitro methods, such as cell and organ culture, computer modelling and modified LD50 tests using lesser number of animals. Specifically in the case of Draize eye irritancy test using rabbits, a number of refinements have been incorporated by different workers, mainly use of a local anaesthetic which will reduce animal distress without vitiating the test results. The author recommends exploration of new avenues for testing based on the advances in cell biology

Complete Genome Sequences of Bacillus subtilis subsp. subtilis Laboratory Strains JH642 (AG174) and AG1839

The Gram-positive bacterium Bacillus subtilis is widely used for studies of cellular and molecular processes. We announce the complete genomic sequences of strain AG174, our stock of the commonly used strain JH642, and strain AG1839, a derivative that contains a mutation in the replication initiation gene dnaB and a linked Tn917.National Institute of General Medical Sciences (U.S.) (NIH award number GM41934

The First Forty Years of the Alternatives Approach: Refining, Reducing, and Replacing the Use of Laboratory Animals

The concept of the Three Rs— reduction, refinement, and replacement of animal use in biomedical experimentation—stems from a project launched in 1954 by a British organization, the Universities Federation for Animal Welfare (UFAW). UFAW commissioned William Russell and Rex Burch to analyze the status of humane experimental techniques involving animals. In 1959 these scientists published a book that set out the principles of the Three Rs, which came to be known as alternative methods. Initially, Russell and Burch’s book was largely ignored, but their ideas were gradually picked up by the animal protection community in the 1960s and early ’70s. In the ’80s, spurred by public pressure, the alternatives approach was incorporated into national legislation throughout the developed countries and embraced by industry in Europe and America. Government centers devoted to the validation and regulatory acceptance of alternative methods were established during the ’90s. By 2000 the use of animals in research had fallen by up to fifty percent from its high in the 1970s

Critical slowing down in polynomial time algorithms

Combinatorial optimization algorithms which compute exact ground state configurations in disordered magnets are seen to exhibit critical slowing down at zero temperature phase transitions. Using arguments based on the physical picture of the model, including vanishing stiffness on scales beyond the correlation length and the ground state degeneracy, the number of operations carried out by one such algorithm, the push-relabel algorithm for the random field Ising model, can be estimated. Some scaling can also be predicted for the 2D spin glass.Comment: 4 pp., 3 fig

Alirocumab in high-risk patients: Observations from the open-label expanded use program

BACKGROUND: The alirocumab expanded use program provided open-label access to alirocumab before its commercial availability to patients with severe hypercholesterolemia not controlled with maximally tolerated doses of standard-of-care lipid-lowering therapy. OBJECTIVE: To describe the safety and lipid-lowering efficacy of alirocumab in high-risk patients who were likely to be early users of proprotein convertase subtilisin/kexin type 9 inhibitors after approval. METHODS: Patients with heterozygous familial hypercholesterolemia (HeFH) and/or coronary heart disease (CHD) and baseline low-density lipoprotein cholesterol (LDL-C) of ≥160 mg/dL on maximally tolerated lipid-lowering therapy were enrolled and received alirocumab 150 mg every 2 weeks for 24 weeks. Patients were permitted use of all available statins; those not taking any dose of statin could also be enrolled. RESULTS: Of 100 enrolled patients, 93 were white, 62 were women, and overall mean age was 58 years; 61 had HeFH, 3 had unknown type of familial hypercholesterolemia, 66 had CHD, and 30 had both familial hypercholesterolemia and CHD. Sixty-four patients were identified by their providers to have some level of statin intolerance; of these, 47 were not on statin. Alirocumab reduced LDL-C on average from 221 mg/dL at baseline to 102 mg/dL by week 24 (-55%). Treatment-emergent adverse events were experienced in 61% of patients and treatment-emergent adverse events leading to permanent treatment discontinuation in 3% of patients; no deaths occurred. CONCLUSIONS: Safety and efficacy observations from the open-label alirocumab expanded use program of very high-risk patients with HeFH and/or CHD and baseline LDL-C of ≥160 mg/dL uncontrolled by maximally tolerated lipid-lowering therapy were consistent with those in the placebo/ezetimibe-controlled ODYSSEY trials

Incident frailty and cognitive impairment by heart failure status in older patients with atrial fibrillation: the SAGE-AF study

Background: Atrial fibrillation (AF) and heart failure (HF) frequently co-occur in older individuals. Among patients with AF, HF increases risks for stroke and death, but the associations between HF and incident cognition and physical impairment remain unknown. We aimed to examine the cross-sectional and prospective associations between HF, cognition, and frailty among older patients with AF. Methods: The SAGE-AF (Systematic Assessment of Geriatric Elements in AF) study enrolled 1244 patients with AF (mean age 76 years, 48% women) from five practices in Massachusetts and Georgia. HF at baseline was identified from electronic health records using ICD-9/10 codes. At baseline and 1-year, frailty was assessed by Cardiovascular Health Survey score and cognition was assessed by the Montreal Cognitive Assessment. Results: Patients with prevalent HF (n = 463, 37.2%) were older, less likely to be non-Hispanic white, had less education, and had greater cardiovascular comorbidity burden and higher CHA2DS2VASC and HAS-BLED scores than patients without HF (all P\u27s \u3c 0.01). In multivariable adjusted regression models, HF (present vs. absent) was associated with both prevalent frailty (adjusted odds ratio [aOR]: 2.38, 95% confidence interval [CI]: 1.64-3.46) and incident frailty at 1 year (aOR: 2.48, 95% CI: 1.37-4.51). HF was also independently associated with baseline cognitive impairment (aOR: 1.60, 95% CI: 1.22-2.11), but not with developing cognitive impairment at 1 year (aOR 1.04, 95%CI: 0.64-1.70). Conclusions: Among ambulatory older patients with AF, the co-existence of HF identifies individuals with physical and cognitive impairments who are at higher short-term risk for becoming frail. Preventive strategies to this vulnerable subgroup merit consideration

Low-energy excitations in the three-dimensional random-field Ising model

The random-field Ising model (RFIM), one of the basic models for quenched disorder, can be studied numerically with the help of efficient ground-state algorithms. In this study, we extend these algorithm by various methods in order to analyze low-energy excitations for the three-dimensional RFIM with Gaussian distributed disorder that appear in the form of clusters of connected spins. We analyze several properties of these clusters. Our results support the validity of the droplet-model description for the RFIM.Comment: 10 pages, 9 figure