Full Text Available Abstract It is one of the central aims of the philosophy of science to elucidate the meanings of scientific terms and also to think critically about their application. The focus of this essay is the scientific term predict and whether there is credible evidence that animal models, especially in toxicology and pathophysiology, can be used to predict human outcomes. Whether animals can be used to predict human response to drugs and other chemicals is apparently a contentious issue. However, when one empirically analyzes animal models using scientific tools they fall far short of being able to predict human responses. This is not surprising considering what we have learned from fields such evolutionary and developmental biology, gene regulation and expression, epigenetics, complexity theory, and comparative genomics.
The weekly body weight measurements of a growing strain of Ross broiler were used to compare the of ability of three mathematical models (the multi, linear, quadratic and Exponential) to predict 8 week body weight from early body measurements at weeks I, II, III, IV, V, VI and VII. The results suggest that the three models ...
Varga, O E; Zsíros, N; Olsson, I A S
For therapeutic studies, predictive validity of animal models - arguably the most important feature of animal models in terms of human relevance - can be calculated retrospectively by obtaining data on treatment efficacy from human and animal trials. Using rosiglitazone as a case study, we aim to determine the predictive validity of animal models of diabetes, by analysing which models perform most similarly to humans during rosiglitazone treatment in terms of changes in standard diabetes diagnosis parameters (glycosylated haemoglobin [HbA1c] and fasting glucose levels). A further objective of this paper was to explore the impact of four covariates on the predictive capacity: (i) diabetes induction method; (ii) drug administration route; (iii) sex of animals and (iv) diet during the experiments. Despite the variable consistency of animal species-based models with the human reference for glucose and HbA1c treatment effects, our results show that glucose and HbA1c treatment effects in rats agreed better with the expected values based on human data than in other species. Induction method was also found to be a substantial factor affecting animal model performance. The study concluded that regular reassessment of animal models can help to identify human relevance of each model and adapt research design for actual research goals. © 2015 World Obesity.
Gøtze, Jens Peter; Krentz, Andrew
In this issue of Cardiovascular Endocrinology, we are proud to present a broad and dedicated spectrum of reviews on animal models in cardiovascular disease. The reviews cover most aspects of animal models in science from basic differences and similarities between small animals and the human...
Herati, Ramin Sedaghat; Wherry, E John
Animal models are an essential feature of the vaccine design toolkit. Although animal models have been invaluable in delineating the mechanisms of immune function, their precision in predicting how well specific vaccines work in humans is often suboptimal. There are, of course, many obvious species differences that may limit animal models from predicting all details of how a vaccine works in humans. However, careful consideration of which animal models may have limitations should also allow more accurate interpretations of animal model data and more accurate predictions of what is to be expected in clinical trials. In this article, we examine some of the considerations that might be relevant to cross-species extrapolation of vaccine-related immune responses for the prediction of how vaccines will perform in humans. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.
Sazykina, Tatiana G
Model predictions of population response to chronic ionizing radiation (endpoint 'morbidity') were made for 11 species of warm-blooded animals, differing in body mass and lifespan - from mice to elephant. Predictions were made also for 3 bird species (duck, pigeon, and house sparrow). Calculations were based on analytical solutions of the mathematical model, simulating a population response to low-LET ionizing radiation in an ecosystem with a limiting resource (Sazykina, Kryshev, 2016). Model parameters for different species were taken from biological and radioecological databases; allometric relationships were employed for estimating some parameter values. As a threshold of decreased health status in exposed populations ('health threshold'), a 10% reduction in self-repairing capacity of organisms was suggested, associated with a decline in ability to sustain environmental stresses. Results of the modeling demonstrate a general increase of population vulnerability to ionizing radiation in animal species of larger size and longevity. Populations of small widespread species (mice, house sparrow; body mass 20-50 g), which are characterized by intensive metabolism and short lifespan, have calculated 'health thresholds' at dose rates about 6.5-7.5 mGy day -1 . Widespread animals with body mass 200-500 g (rat, common pigeon) - demonstrate 'health threshold' values at 4-5 mGy day -1 . For populations of animals with body mass 2-5 kg (rabbit, fox, raccoon), the indicators of 10% health decrease are in the range 2-3.4 mGy day -1 . For animals with body mass 40-100 kg (wolf, sheep, wild boar), thresholds are within 0.5-0.8 mGy day -1 ; for herbivorous animals with body mass 200-300 kg (deer, horse) - 0.5-0.6 mGy day -1 . The lowest health threshold was estimated for elephant (body mass around 5000 kg) - 0.1 mGy day -1 . According to the model results, the differences in population sensitivities of warm-blooded animal species to ionizing radiation are generally
Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans (Presented by James McKim, Ph.D., DABT, Founder and Chief Science Officer, CeeTox) (5/25/2012)
Jacobsen, Kirsten Rosenmaj; Jørgensen, Pernille Schønning; Pipper, Christian Bressen
The aim of the present study was to evaluate the utility of various non-invasive parameters for the prediction of tumor development and animal welfare in a murine xenograft model in male C.B-17 SCID (C.B-Igh-1(b)/IcrTac-Prkdc(scid)) mice. The study showed that body weight, food and water consumpt......The aim of the present study was to evaluate the utility of various non-invasive parameters for the prediction of tumor development and animal welfare in a murine xenograft model in male C.B-17 SCID (C.B-Igh-1(b)/IcrTac-Prkdc(scid)) mice. The study showed that body weight, food and water...... consumption, and an animal welfare assessment (AWA) protocol revealed marked differences between control and cancer lines as the size of the tumor increased. However, only the AWA protocol was effective in predicting the tumor size and the level of fecal corticosterone metabolites (FCM). FCM levels were......, however, negatively-correlated to the AWA score, and the tumor size, both when evaluated on a given day and when accumulated over the entire period. In conclusion, the present study demonstrated that body weight and food and water consumption were negatively-affected as tumor developed but only the animal...
Jones, CA; Watson, DJG; Fone, KCF
Developing reliable, predictive animal models for complex psychiatric disorders, such as schizophrenia, is essential to increase our understanding of the neurobiological basis of the disorder and for the development of novel drugs with improved therapeutic efficacy. All available animal models of schizophrenia fit into four different induction categories: developmental, drug-induced, lesion or genetic manipulation, and the best characterized examples of each type are reviewed herein. Most rodent models have behavioural phenotype changes that resemble ‘positive-like’ symptoms of schizophrenia, probably reflecting altered mesolimbic dopamine function, but fewer models also show altered social interaction, and learning and memory impairment, analogous to negative and cognitive symptoms of schizophrenia respectively. The negative and cognitive impairments in schizophrenia are resistant to treatment with current antipsychotics, even after remission of the psychosis, which limits their therapeutic efficacy. The MATRICS initiative developed a consensus on the core cognitive deficits of schizophrenic patients, and recommended a standardized test battery to evaluate them. More recently, work has begun to identify specific rodent behavioural tasks with translational relevance to specific cognitive domains affected in schizophrenia, and where available this review focuses on reporting the effect of current and potential antipsychotics on these tasks. The review also highlights the need to develop more comprehensive animal models that more adequately replicate deficits in negative and cognitive symptoms. Increasing information on the neurochemical and structural CNS changes accompanying each model will also help assess treatments that prevent the development of schizophrenia rather than treating the symptoms, another pivotal change required to enable new more effective therapeutic strategies to be developed. LINKED ARTICLES This article is part of a themed issue on
Larsen, Malte Selch; Juul, Rasmus Vestergaard; Groth, Andreas Velsing
for nonlinear kinetics and gender-specific difference in clearance for rFVIII. The predictive performance of the animal population PK models of rFVIIa and rFVIII revealed significant species-variation. The developed PK models of rFVIIa and rFVIII in monkeys and dogs along with allometric interspecies scaling......Various experimental animal models are used in haemophilia research, however, little is known about how well the different species predict pharmacokinetic (PK) profiles in haemophilia patients. The aim of the current study was to describe the plasma concentration-time profile of recombinant...... activated factor VII (rFVIIa) and recombinant factor VIII (rFVIII) in several experimental animal models using population PK modelling, and apply a simulation-based approach to evaluate how well the developed animal population PK models predict human PK. PK models were developed for rFVIIa and r...
Passini, Elisa; Britton, Oliver J; Lu, Hua Rong; Rohrbacher, Jutta; Hermans, An N; Gallacher, David J; Greig, Robert J H; Bueno-Orovio, Alfonso; Rodriguez, Blanca
Early prediction of cardiotoxicity is critical for drug development. Current animal models raise ethical and translational questions, and have limited accuracy in clinical risk prediction. Human-based computer models constitute a fast, cheap and potentially effective alternative to experimental assays, also facilitating translation to human. Key challenges include consideration of inter-cellular variability in drug responses and integration of computational and experimental methods in safety pharmacology. Our aim is to evaluate the ability of in silico drug trials in populations of human action potential (AP) models to predict clinical risk of drug-induced arrhythmias based on ion channel information, and to compare simulation results against experimental assays commonly used for drug testing. A control population of 1,213 human ventricular AP models in agreement with experimental recordings was constructed. In silico drug trials were performed for 62 reference compounds at multiple concentrations, using pore-block drug models (IC 50 /Hill coefficient). Drug-induced changes in AP biomarkers were quantified, together with occurrence of repolarization/depolarization abnormalities. Simulation results were used to predict clinical risk based on reports of Torsade de Pointes arrhythmias, and further evaluated in a subset of compounds through comparison with electrocardiograms from rabbit wedge preparations and Ca 2+ -transient recordings in human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). Drug-induced changes in silico vary in magnitude depending on the specific ionic profile of each model in the population, thus allowing to identify cell sub-populations at higher risk of developing abnormal AP phenotypes. Models with low repolarization reserve (increased Ca 2+ /late Na + currents and Na + /Ca 2+ -exchanger, reduced Na + /K + -pump) are highly vulnerable to drug-induced repolarization abnormalities, while those with reduced inward current density
Full Text Available Early prediction of cardiotoxicity is critical for drug development. Current animal models raise ethical and translational questions, and have limited accuracy in clinical risk prediction. Human-based computer models constitute a fast, cheap and potentially effective alternative to experimental assays, also facilitating translation to human. Key challenges include consideration of inter-cellular variability in drug responses and integration of computational and experimental methods in safety pharmacology. Our aim is to evaluate the ability of in silico drug trials in populations of human action potential (AP models to predict clinical risk of drug-induced arrhythmias based on ion channel information, and to compare simulation results against experimental assays commonly used for drug testing. A control population of 1,213 human ventricular AP models in agreement with experimental recordings was constructed. In silico drug trials were performed for 62 reference compounds at multiple concentrations, using pore-block drug models (IC50/Hill coefficient. Drug-induced changes in AP biomarkers were quantified, together with occurrence of repolarization/depolarization abnormalities. Simulation results were used to predict clinical risk based on reports of Torsade de Pointes arrhythmias, and further evaluated in a subset of compounds through comparison with electrocardiograms from rabbit wedge preparations and Ca2+-transient recordings in human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs. Drug-induced changes in silico vary in magnitude depending on the specific ionic profile of each model in the population, thus allowing to identify cell sub-populations at higher risk of developing abnormal AP phenotypes. Models with low repolarization reserve (increased Ca2+/late Na+ currents and Na+/Ca2+-exchanger, reduced Na+/K+-pump are highly vulnerable to drug-induced repolarization abnormalities, while those with reduced inward current density
Collins, Lisa M.; Part, Chérie E.
Simple Summary In this review paper we discuss the different modeling techniques that have been used in animal welfare research to date. We look at what questions they have been used to answer, the advantages and pitfalls of the methods, and how future research can best use these approaches to answer some of the most important upcoming questions in farm animal welfare. Abstract The use of models in the life sciences has greatly expanded in scope and advanced in technique in recent decades. However, the range, type and complexity of models used in farm animal welfare is comparatively poor, despite the great scope for use of modeling in this field of research. In this paper, we review the different modeling approaches used in farm animal welfare science to date, discussing the types of questions they have been used to answer, the merits and problems associated with the method, and possible future applications of each technique. We find that the most frequently published types of model used in farm animal welfare are conceptual and assessment models; two types of model that are frequently (though not exclusively) based on expert opinion. Simulation, optimization, scenario, and systems modeling approaches are rarer in animal welfare, despite being commonly used in other related fields. Finally, common issues such as a lack of quantitative data to parameterize models, and model selection and validation are discussed throughout the review, with possible solutions and alternative approaches suggested. PMID:26487411
Full Text Available Preclinical studies to predict the efficacy and safety of drugs have conventionally been conducted almost exclusively in mice and rats as rodents, despite the differences in drug metabolism between humans and rodents. Furthermore, human (ℎ viruses such as hepatitis viruses do not infect the rodent liver. A mouse bearing a liver in which the hepatocytes have been largely repopulated with ℎ-hepatocytes would overcome some of these disadvantages. We have established a practical, efficient, and large-scale production system for such mice. Accumulated evidence has demonstrated that these hepatocyte-humanized mice are a useful and reliable animal model, exhibiting ℎ-type responses in a series of in vivo drug processing (adsorption, distribution, metabolism, excretion experiments and in the infection and propagation of hepatic viruses. In this review, we present the current status of studies on chimeric mice and describe their usefulness in the study of peroxisome proliferator-activated receptors.
Olsson, I. Anna S.; Sandøe, Peter
This chapter aims to encourage scientists and others interested in the use of animal models of disease – specifically, in the study of dementia – to engage in ethical reflection. It opens with a general discussion of the moral acceptability of animal use in research. Three ethical approaches are ...
Olsson, I. Anna S.; Sandøe, Peter
This chapter aims to encourage scientists and others interested in the use of animal models of disease – specifically, in the study of dementia – to engage in ethical reflection. It opens with a general discussion of the moral acceptability of animal use in research. Three ethical approaches...
Greater susceptibility to infection is a hallmark of compromised immune function in humans and animals, and is often considered the benchmark against which the predictive value of immune function tests are compared. This focus of this paper is resistance to infection with the pa...
Horton, H.M.; Calabrese, E.J.
The use of Dorset sheep erythrocytes as a model for human G-6-PD deficient erythrocytes was investigated. Seven pharmaceuticals were examined for oxidant stressor effects using a liver microsomal enzyme system to generate metabolites of the drugs. The pharmaceuticals examined were salicyclic acid, dapsone, naphthalene, B-naphtol, p-aminobenzoic acid, sulfanilamide and sulfapyridine. The test compounds were incubated with Dorset sheep erythrocytes and oxidant stressor effects were measured through reduced glutathione (GSH) levels and methemaglobin formation. The response of the Dorset sheep erythrocytes to the seven agents was compared to previous studies revealing the response of human G-6-PD deficient erythrocytes to these agents. The results indicated that metabolites of the pharmaceuticals, B-naphthol, dapsone, and sulfanilamide, are oxidant stressor agents towards sheep G-6-PD deficient erythrocytes. These results agreed with studies on the response of human G-6-PD deficient erythrocytes. The metabolized naphthalene and sulfapyridine did not cause oxidant stress in the sheep erythrocytes, despite the fact that these two agents caused oxidizing effects in human G-6-PD deficient erythrocytes in previous studies. None of the non-metabolized parent compounds caused oxidant stress in the sheep erythrocytes, which agreed with the responses of human G-6-PD deficient erythrocytes.
Brozoski, Thomas J; Bauer, Carol A
Presented is a thematic review of animal tinnitus models from a functional perspective. Chronic tinnitus is a persistent subjective sound sensation, emergent typically after hearing loss. Although the sensation is experientially simple, it appears to have central a nervous system substrate of unexpected complexity that includes areas outside of those classically defined as auditory. Over the past 27 years animal models have significantly contributed to understanding tinnitus' complex neurophysiology. In that time, a diversity of models have been developed, each with its own strengths and limitations. None has clearly become a standard. Animal models trace their origin to the 1988 experiments of Jastreboff and colleagues. All subsequent models derive some of their features from those experiments. Common features include behavior-dependent psychophysical determination, acoustic conditions that contrast objective sound and silence, and inclusion of at least one normal-hearing control group. In the present review, animal models have been categorized as either interrogative or reflexive. Interrogative models use emitted behavior under voluntary control to indicate hearing. An example would be pressing a lever to obtain food in the presence of a particular sound. In this type of model animals are interrogated about their auditory sensations, analogous to asking a patient, "What do you hear?" These models require at least some training and motivation management, and reflect the perception of tinnitus. Reflexive models, in contrast, employ acoustic modulation of an auditory reflex, such as the acoustic startle response. An unexpected loud sound will elicit a reflexive motor response from many species, including humans. Although involuntary, acoustic startle can be modified by a lower-level preceding event, including a silent sound gap. Sound-gap modulation of acoustic startle appears to discriminate tinnitus in animals as well as humans, and requires no training or
Hu, Yijie; Yibrehu, Betel; Zabini, Diana; Kuebler, Wolfgang M
Sarcoidosis is a debilitating, inflammatory, multiorgan, granulomatous disease of unknown cause, commonly affecting the lung. In contrast to other chronic lung diseases such as interstitial pulmonary fibrosis or pulmonary arterial hypertension, there is so far no widely accepted or implemented animal model for this disease. This has hampered our insights into the etiology of sarcoidosis, the mechanisms of its pathogenesis, the identification of new biomarkers and diagnostic tools and, last not least, the development and implementation of novel treatment strategies. Over past years, however, a number of new animal models have been described that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outline the present status quo for animal models of sarcoidosis, comparing their pros and cons with respect to their ability to mimic the etiological, clinical and histological hallmarks of human disease and discuss their applicability for future research. Overall, the recent surge in animal models has markedly expanded our options for translational research; however, given the relative early stage of most animal models for sarcoidosis, appropriate replication of etiological and histological features of clinical disease, reproducibility and usefulness in terms of identification of new therapeutic targets and biomarkers, and testing of new treatments should be prioritized when considering the refinement of existing or the development of new models.
Rachida A. Bouhenni
Full Text Available Glaucoma is a heterogeneous group of disorders that progressively lead to blindness due to loss of retinal ganglion cells and damage to the optic nerve. It is a leading cause of blindness and visual impairment worldwide. Although research in the field of glaucoma is substantial, the pathophysiologic mechanisms causing the disease are not completely understood. A wide variety of animal models have been used to study glaucoma. These include monkeys, dogs, cats, rodents, and several other species. Although these models have provided valuable information about the disease, there is still no ideal model for studying glaucoma due to its complexity. In this paper we present a summary of most of the animal models that have been developed and used for the study of the different types of glaucoma, the strengths and limitations associated with each species use, and some potential criteria to develop a suitable model.
Kori, Hiroshi; Yamaguchi, Yoshiaki; Okamura, Hitoshi
The endogenous circadian clock drives oscillations that are completely synchronized with the environmental day-night rhythms with a period of approximately 24 hours. Temporal misalignment between one’s internal circadian clock and the external solar time often occurs in shift workers and long-distance travelers; such misalignments are accompanied by sleep disturbances and gastrointestinal distress. Repeated exposure to jet lag and rotating shift work increases the risk of lifestyle-related diseases, such as cardiovascular complaints and metabolic insufficiencies. However, the mechanism behind the disruption of one’s internal clock is not well understood. In this paper, we therefore present a new theoretical concept called “jet lag separatrix” to understand circadian clock disruption and slow recovery from jet lag based on the mathematical model describing the hierarchical structure of the circadian clock. To demonstrate the utility of our theoretical study, we applied it to predict that re-entrainment via a two-step jet lag in which a four-hour shift of the light-dark cycle is given in the span of two successive days requires fewer days than when given as a single eight-hour shift. We experimentally verified the feasibility of our theory in C57BL/6 strain mice, with results indicating that this pre-exposure of jet lag is indeed beneficial.
1 Dept.of Veterinary Surgery and Medicine 2Veterinary Teaching Hospital Ahmadu Bello University. Zaria .... unnecessary suffering., Administration of poisons .... way that humans are. Vivisection/ Surgical Training And Research. Animal model use: In both the human and veterinary medical practice, there continue to be ...
The metabolic theory of ecology (MTE) predicts observed patterns in ecology based on metabolic rates of individuals. The theory is influential but also criticized for a lack of firm empirical evidence confirming MTE's quantitative predictions of processes, e.g. outcome of competition, at population or community level. Self-thinning is a well-known population level phenomenon among plants, but a much less studied phenomenon in animal populations and no consensus exists on what a universal thinning slope for animal populations might be, or if it exists. The goal of this study was to use animal self-thinning as a tool to test population-level predictions from MTE, by analysing (i) if self-thinning can be induced in populations of house crickets (Acheta domesticus) and (ii) if the resulting thinning trajectories can be predicted from metabolic theory, using estimates of the species-specific metabolic rate of A. domesticus. I performed a laboratory study where the growth of A. domesticus was followed, from hatching until emergence as adults, in 71 cohorts of five different starting densities. Ninety-six per cent of all cohorts in the three highest starting densities showed evidence of self-thinning, with estimated thinning slopes in general being remarkably close to that expected under metabolic constraints: A cross-sectional analysis of all data showing evidence of self-thinning produced an ordinary least square (OLS) slope of -1·11, exactly that predicted from specific metabolic allometry of A. domesticus. This result is furthermore supported by longitudinal analyses, allowing for independent responses within cohorts, producing a mean OLS slope across cohorts of -1·13 and a fixed effect linear mixed effects models slope of -1·09. Sensitivity analysis showed that these results are robust to how the criterion for on-going self-thinning was defined. Finally, also as predicted by metabolic theory, temperature had a negative effect on the thinning intercept, producing
Fink, Mitchell P
Sepsis remains a common, serious, and heterogeneous clinical entity that is difficult to define adequately. Despite its importance as a public health problem, efforts to develop and gain regulatory approval for a specific therapeutic agent for the adjuvant treatment of sepsis have been remarkably unsuccessful. One step in the critical pathway for the development of a new agent for adjuvant treatment of sepsis is evaluation in an appropriate animal model of the human condition. Unfortunately, the animal models that have been used for this purpose have often yielded misleading findings. It is likely that there are multiple reasons for the discrepancies between the results obtained in tests of pharmacological agents in animal models of sepsis and the outcomes of human clinical trials. One of important reason may be that the changes in gene expression, which are triggered by trauma or infection, are different in mice, a commonly used species for preclinical testing, and humans. Additionally, many species, including mice and baboons, are remarkably resistant to the toxic effects of bacterial lipopolysaccharide, whereas humans are exquisitely sensitive. New approaches toward the use of animals for sepsis research are being investigated. But, at present, results from preclinical studies of new therapeutic agents for sepsis must be viewed with a degree of skepticism.
Getz, Godfrey S.; Reardon, Catherine A.
Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to manipulation of the atherogenic process and modeling human atherosclerosis or lipoprotein profile. Useful large animal models include pigs, rabbits and non-human primates. Due in large part to the relative ease of genetic manipulation and the relatively short time frame for the development of atherosclerosis, murine models are currently the most extensively used. While not all aspects of murine atherosclerosis are identical to humans, studies using murine models have suggested potential biological processes and interactions that underlie this process. As it becomes clear that different factors may influence different stages of lesion development, the use of mouse models with the ability to turn on or delete proteins or cells in tissue specific and temporal manner will be very valuable. PMID:22383700
Lories, Rik J U
The aim of this article is to review new insights into spondyloarthritis obtained in animal models during the last year. HLA-B27 misfolding has been demonstrated in HLA-B27/human beta2-microglobulin transgenic rats. HLA-B27 misfolding is associated with a typical unfolded protein stress response and with an interferon-response signature. Prebiotic treatment of these rats reduced colitis and arthritis. Proteoglycan-induced spondylitis is distinct from proteoglycan-induced arthritis. Specific susceptibility loci for proteoglycan-induced spondylitis have been demonstrated. Bone morphogenetic proteins are important in new cartilage and bone formation in ankylosing enthesitis. Psoriasis and psoriatic arthritis-like disease develops in conditional double JunB/c-Jun knockout mice. Insights into the molecular signaling pathways driving HLA-B27 associated spondylitis, autoimmune spondylitis, ankylosing enthesitis and psoriasis, resulting from animal models, identify new and specific therapeutic targets in spondyloarthritis.
Fink, Mitchell P
Sepsis remains a common, serious, and heterogeneous clinical entity that is difficult to define adequately. Despite its importance as a public health problem, efforts to develop and gain regulatory approval for a specific therapeutic agent for the adjuvant treatment of sepsis have been remarkably unsuccessful. One step in the critical pathway for the development of a new agent for adjuvant treatment of sepsis is evaluation in an appropriate animal model of the human condition. Unfortunately, ...
Sabatino, Denise E.; Nichols, Timothy C.; Merricks, Elizabeth; Bellinger, Dwight A.; Herzog, Roland W.; Monahan, Paul E.
The X-linked bleeding disorder hemophilia is caused by mutations in coagulation factor VIII (hemophilia A) or factor IX (hemophilia B). Unless prophylactic treatment is provided, patients with severe disease (less than 1% clotting activity) typically experience frequent spontaneous bleeds. Current treatment is largely based on intravenous infusion of recombinant or plasma-derived coagulation factor concentrate. More effective factor products are being developed. Moreover, gene therapies for sustained correction of hemophilia are showing much promise in pre-clinical studies and in clinical trials. These advances in molecular medicine heavily depend on availability of well-characterized small and large animal models of hemophilia, primarily hemophilia mice and dogs. Experiments in these animals represent important early and intermediate steps of translational research aimed at development of better and safer treatments for hemophilia, such a protein and gene therapies or immune tolerance protocols. While murine models are excellent for studies of large groups of animals using genetically defined strains, canine models are important for testing scale-up and for longer-term follow-up as well as for studies that require larger blood volumes. PMID:22137432
Baudracco, J; Lopez-Villalobos, N; Holmes, C W; Comeron, E A; Macdonald, K A; Barry, T N; Friggens, N C
This animal simulation model, named e-Cow, represents a single dairy cow at grazing. The model integrates algorithms from three previously published models: a model that predicts herbage dry matter (DM) intake by grazing dairy cows, a mammary gland model that predicts potential milk yield and a body lipid model that predicts genetically driven live weight (LW) and body condition score (BCS). Both nutritional and genetic drives are accounted for in the prediction of energy intake and its partitioning. The main inputs are herbage allowance (HA; kg DM offered/cow per day), metabolisable energy and NDF concentrations in herbage and supplements, supplements offered (kg DM/cow per day), type of pasture (ryegrass or lucerne), days in milk, days pregnant, lactation number, BCS and LW at calving, breed or strain of cow and genetic merit, that is, potential yields of milk, fat and protein. Separate equations are used to predict herbage intake, depending on the cutting heights at which HA is expressed. The e-Cow model is written in Visual Basic programming language within Microsoft Excel®. The model predicts whole-lactation performance of dairy cows on a daily basis, and the main outputs are the daily and annual DM intake, milk yield and changes in BCS and LW. In the e-Cow model, neither herbage DM intake nor milk yield or LW change are needed as inputs; instead, they are predicted by the e-Cow model. The e-Cow model was validated against experimental data for Holstein-Friesian cows with both North American (NA) and New Zealand (NZ) genetics grazing ryegrass-based pastures, with or without supplementary feeding and for three complete lactations, divided into weekly periods. The model was able to predict animal performance with satisfactory accuracy, with concordance correlation coefficients of 0.81, 0.76 and 0.62 for herbage DM intake, milk yield and LW change, respectively. Simulations performed with the model showed that it is sensitive to genotype by feeding environment
García Pardo, María Pilar; Roger Sánchez, Concepción; De la Rubia Ortí, José Enrique; Aguilar Calpe, María Asunción
The development of animal models of drug reward and addiction is an essential factor for progress in understanding the biological basis of this disorder and for the identification of new therapeutic targets. Depending on the component of reward to be studied, one type of animal model or another may be used. There are models of reinforcement based on the primary hedonic effect produced by the consumption of the addictive substance, such as the self-administration (SA) and intracranial self-stimulation (ICSS) paradigms, and there are models based on the component of reward related to associative learning and cognitive ability to make predictions about obtaining reward in the future, such as the conditioned place preference (CPP) paradigm. In recent years these models have incorporated methodological modifications to study extinction, reinstatement and reconsolidation processes, or to model specific aspects of addictive behavior such as motivation to consume drugs, compulsive consumption or drug seeking under punishment situations. There are also models that link different reinforcement components or model voluntary motivation to consume (two-bottle choice, or drinking in the dark tests). In short, innovations in these models allow progress in scientific knowledge regarding the different aspects that lead individuals to consume a drug and develop compulsive consumption, providing a target for future treatments of addiction.
Medel-Matus, Jesús-Servando; Shin, Don; Sankar, Raman; Mazarati, Andrey
The objective was to determine whether the depression comorbid with epilepsy could be predicted based on inherent premorbid patterns of monoaminergic transmission. In male Wistar rats, despair-like and anhedonia-like behaviors were examined using forced swimming and taste preference tests, respectively. Serotonergic raphe nucleus (RN)-prefrontal cortex (PFC) and dopaminergic ventral tegmental area (VTA)-nucleus accumbens (NAcc) pathways were interrogated by fast scan cyclic voltammetry (FSCV). The assays were performed before and 2 months after pilocarpine status epilepticus. In a subset of naive rats, FSCV, coupled with the intensity-dependent stimulation paradigm, detected specific deviations in each pathway (six rats for RN-PFC and seven rats for VTA-NAcc, with overlap in two, of 19 total subjects) in the absence of behavioral impairments. During epilepsy, animals with preexisting deviations in RN-PFC invariably developed despair, and rats with deviations in VTA-NAcc developed anhedonia. Serotonergic and dopaminergic pathways, respectively, showed signs of explicit deterioration. We suggest that epilepsy triggers decompensations in the already vulnerable depression-relevant neuronal circuits, which culminate in depression. The established connection between the identified specific signatures in monoamine transmission in naive rats and specific symptoms of epilepsy-associated depression may help in understanding causes of comorbidity and in developing its early biomarkers. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
Nestler, Eric J.; Hyman, Steven E.
Modeling of human neuropsychiatric disorders in animals is extremely challenging given the subjective nature of many key symptoms, the lack of biomarkers and objective diagnostic tests, and the early state of the relevant neurobiology and genetics. Nonetheless, progress in understanding pathophysiology and in treatment development would benefit greatly from improved animal models. Here we review the current state of animal models of mental illness, with a focus on schizophrenia, depression, and bipolar disorder. We argue for areas of focus that might increase the likelihood of creating more useful models, at least for some disorders, and for explicit guidelines when animal models are reported. PMID:20877280
Full Text Available Abstract Background After the earthquake on 14, April 2010 at Yushu in China, a plague epidemic hosted by Himalayan marmot (Marmota himalayana became a major public health concern during the reconstruction period. A rapid assessment of the distribution of Himalayan marmot in the area was urgent. The aims of this study were to analyze the relationship between environmental factors and the distribution of burrow systems of the marmot and to predict the distribution of marmots. Methods Two types of marmot burrows (hibernation and temporary in Yushu County were investigated from June to September in 2011. The location of every burrow was recorded with a global positioning system receiver. An ecological niche model was used to determine the relationship between the burrow occurrence data and environmental variables, such as land surface temperature (LST in winter and summer, normalized difference vegetation index (NDVI in winter and summer, elevation, and soil type. The predictive accuracies of the models were assessed by the area under the curve of the receiving operator curve. Results The models for hibernation and temporary burrows both performed well. The contribution orders of the variables were LST in winter and soil type, NDVI in winter and elevation for the hibernation burrow model, and LST in summer, NDVI in summer, soil type and elevation in the temporary burrow model. There were non-linear relationships between the probability of burrow presence and LST, NDVI and elevation. LST of 14 and 23 °C, NDVI of 0.22 and 0.60, and 4100 m were inflection points. A substantially higher probability of burrow presence was observed in swamp soil and dark felty soil than in other soil types. The potential area for hibernation burrows was 5696 km2 (37.7 % of Yushu County, and the area for temporary burrows was 7711 km2 (51.0 % of Yushu County. Conclusions The results suggested that marmots preferred warm areas with relatively low altitudes and good
Karacaoren, B; Janss, L L G; Kadarmideen, H N
May 2004-March 2005 for 7 times approximately at monthly intervals from dairy cows (n=80) stationed at the Chamau research farm of Eidgenössische Technische Hochschule (ETH), Switzerland. Benefits of KF were demonstrated using random walk models via simulations. Breeding values were predicted over...... be useful in animal breeding industry for obtaining online estimation of breeding values over days in milk....
Conti, Heather R.; Huppler, Anna R.; Whibley, Natasha; Gaffen, Sarah L.
Multiple forms of candidiasis are clinically important in humans. Established murine models of disseminated, oropharyngeal, vaginal, and cutaneous candidiasis caused by Candida albicans are described in this unit. Detailed materials and methods for C. albicans growth and detection are also described. PMID:24700323
Marquart, Mary E.
Bacterial keratitis is a disease of the cornea characterized by pain, redness, inflammation, and opacity. Common causes of this disease are Pseudomonas aeruginosa and Staphylococcus aureus. Animal models of keratitis have been used to elucidate both the bacterial factors and the host inflammatory response involved in the disease. Reviewed herein are animal models of bacterial keratitis and some of the key findings in the last several decades. PMID:21274270
Rust, J H
The use of animal models for the study of human disease is, for the most part, a recent development. This discussion of the use of animal models for human diseases directs attention to the sterile period, early advances, some personal experiences, the human as the model, biological oddities among common laboratory animals, malignancies in laboratory animals, problems created by federal regulations, cancer tests with animals, and what the future holds in terms of the use of animal models as an aid to understanding human disease. In terms of early use of animal models, there was a school of rabbis, some of whom were also physicians, in Babylon who studied and wrote extensively on ritual slaughter and the suitability of birds and beasts for food. Considerable detailed information on animal pathology, physiology, anatomy, and medicine in general can be found in the Soncino Babylonian Talmudic Translations. The 1906 edition of the "Jewish Encyclopedia," has been a rich resource. Although it has not been possible to establish what diseases of animals were studied and their relationship to the diseases of humans, there are fascinating clues to pursue, despite the fact that these were sterile years for research in medicine. The quotation from the Talmud is of interest: "The medical knowledge of the Talmudist was based upon tradition, the dissection of human bodies, observation of disease and experiments upon animals." A bright light in the lackluster years of medical research was provided by Galen, considered the originator of research in physiology and anatomy. His dissection of animals and work on apes and other lower animals were models for human anatomy and physiology and the bases for many treatises. Yet, Galen never seemed to suggest that animals could serve as models for human diseases. Most early physicians who can be considered to have been students of disease developed their medical knowledge by observing the sick under their care. 1 early medical investigator
Schaeffel, Frank; Feldkaemper, Marita
Our current understanding of the development of refractive errors, in particular myopia, would be substantially limited had Wiesel and Raviola not discovered by accident that monkeys develop axial myopia as a result of deprivation of form vision. Similarly, if Josh Wallman and colleagues had not found that simple plastic goggles attached to the chicken eye generate large amounts of myopia, the chicken model would perhaps not have become such an important animal model. Contrary to previous assumptions about the mechanisms of myopia, these animal models suggested that eye growth is visually controlled locally by the retina, that an afferent connection to the brain is not essential and that emmetropisation uses more sophisticated cues than just the magnitude of retinal blur. While animal models have shown that the retina can determine the sign of defocus, the underlying mechanism is still not entirely clear. Animal models have also provided knowledge about the biochemical nature of the signal cascade converting the output of retinal image processing to changes in choroidal thickness and scleral growth; however, a critical question was, and still is, can the results from animal models be applied to myopia in children? While the basic findings from chickens appear applicable to monkeys, some fundamental questions remain. If eye growth is guided by visual feedback, why is myopic development not self-limiting? Why does undercorrection not arrest myopic progression even though positive lenses induce myopic defocus, which leads to the development of hyperopia in emmetropic animals? Why do some spectacle or contact lens designs reduce myopic progression and others not? It appears that some major differences exist between animals reared with imposed defocus and children treated with various optical corrections, although without the basic knowledge obtained from animal models, we would be lost in an abundance of untestable hypotheses concerning human myopia. © 2015 Optometry
Lines, K.E.; Stevenson, M.; Thakker, R.V.
Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal mod...
Dei-Cas, E.; Brun-Pascaud, M.; Bille-Hansen, Vivi
As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research. The parasite was reported in numerous mammals but P. carinii pneumonia (PCP) experimental models were...... a source of parasites taxonomically related to P. carinii sp. f hominis. Moreover, primates might be used as experimental hosts to human Pneumocystis. A marked variability of parasite levels among corticosteroid-treated animals and the fact that the origin of the parasite strain remains unknown......, are important drawbacks of the corticosteroid-treated models. For these reasons, inoculated animal models of PCP were developed. The intratracheal inoculation of lung homogenates containing viable parasites in corticosteroid-treated non-latently infected rats resulted in extensive, reproducible Pneumocystis...
Lines, K.E.; Stevenson, M.; Thakker, R.V.
Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies. PMID:26320859
Wu, X; Lund, M S; Sun, D; Zhang, Q; Su, G
One of the factors affecting the reliability of genomic prediction is the relationship among the animals of interest. This study investigated the reliability of genomic prediction in various scenarios with regard to the relationship between test and training animals, and among animals within the training data set. Different training data sets were generated from EuroGenomics data and a group of Nordic Holstein bulls (born in 2005 and afterwards) as a common test data set. Genomic breeding values were predicted using a genomic best linear unbiased prediction model and a Bayesian mixture model. The results showed that a closer relationship between test and training animals led to a higher reliability of genomic predictions for the test animals, while a closer relationship among training animals resulted in a lower reliability. In addition, the Bayesian mixture model in general led to a slightly higher reliability of genomic prediction, especially for the scenario of distant relationships between training and test animals. Therefore, to prevent a decrease in reliability, constant updates of the training population with animals from more recent generations are required. Moreover, a training population consisting of less-related animals is favourable for reliability of genomic prediction. © 2015 Blackwell Verlag GmbH.
Sekimizu, N; Paudel, A; Hamamoto, H
Sacrificing model animals is required for developing effective drugs before being used in human beings. In Japan today, at least 4,210,000 mice and other mammals are sacrificed to a total of 6,140,000 per year for the purpose of medical studies. All the animals treated in Japan, including test animals, are managed under control of "Act on Welfare and Management of Animals". Under the principle of this Act, no person shall kill, injure, or inflict cruelty on animals without due cause. "Animal" addressed in the Act can be defined as a "vertebrate animal". If we can make use of invertebrate animals in testing instead of vertebrate ones, that would be a remarkable solution for the issue of animal welfare. Furthermore, there are numerous advantages of using invertebrate animal models: less space and small equipment are enough for taking care of a large number of animals and thus are cost-effective, they can be easily handled, and many biological processes and genes are conserved between mammals and invertebrates. Today, many invertebrates have been used as animal models, but silkworms have many beneficial traits compared to mammals as well as other insects. In a Genome Pharmaceutical Institute's study, we were able to achieve a lot making use of silkworms as model animals. We would like to suggest that pharmaceutical companies and institutes consider the use of the silkworm as a model animal which is efficacious both for financial value by cost cutting and ethical aspects in animals' welfare.
Organ transplantation has become a successful and acceptable treatment for end-stage organ failure. Such success has allowed transplant patients to resume a normal lifestyle. The demands for transplantation have been steadily increasing, as more patients and new diseases are being deemed eligible for treatment via transplantation. However, it is clear that human organs will never meet the increasing demand of transplantation. Therefore, scientists must continue to pursue alternative therapies and explore new treatments to meet the growing demand for the limited number of organs available. Transplanting organs from animals into humans (xenotransplantation) is one such therapy. The observed enthusiasm for xenotransplantation, irrespective of the severe shortage of human organs and tissues available for transplantation, can be said to stem from at least two factors. First, there is the possibility that animal organs and tissues might be less susceptible than those of humans to the recurrence of disease processes. Second, a xenograft might be used as a vehicle for introducing novel genes or biochemical processes which could be of therapeutic value for the transplant recipient.To date, millions of lives have been saved by organ transplantation. These remarkable achievements would have been impossible without experimental transplantation research in animal models. Presently, more than 95% of organ transplantation research projects are carried out using rodents, such as rats and mice. The key factor to ensure the success of these experiments lies in state-of-the art experimental surgery. Small animal models offer unique advantages for the mechanistic study of xenotransplantation rejection. Currently, multiple models have been developed for investigating the different stages of immunological barriers in xenotransplantation. In this chapter, we describe six valuable small animal models that have been used in xenotransplantation research. The methodology for the small animal
Han, Nayoung; Chae, Jung-Woo; Jeon, Jihyun; Lee, Jaeyeon; Back, Hyun-Moon; Song, Byungjeong; Kwon, Kwang-Il; Kim, Sang Kyum; Yun, Hwi-Yeol
Although alterations in the methionine metabolism cycle (MMC) have been associated with vascular complications of diabetes, there have not been consistent results about the levels of methionine and homocysteine in type 2 diabetes mellitus (T2DM). The aim of the current study was to predict changes in plasma methionine and homocysteine concentrations after simulated consumption of methionine-rich foods, following the development of a mathematical model for MMC in Zucker Diabetic Fatty (ZDF) rats, as a representative T2DM animal model. The model building and simulation were performed using NONMEM® (ver. 7.3.0) assisted by Perl-Speaks-NONMEM (PsN, ver. 4.3.0). Model parameters were derived using first-order conditional estimation method with interactions permitted among the parameters (FOCE-INTER). NCA was conducted using Phoenix (ver. 6.4.0). For all tests, we considered a P -value < 0.05 to reflect statistical significance. Our model featured seven compartments that considered all parts of the cycle by applying non-linear mixed effects model. Conversion of S-adenosyl-L-homocysteine (SAH) to homocysteine increased and the metabolism of homocysteine was reduced under diabetic conditions, and consequently homocysteine accumulated in the elimination phase.Using our model, we performed simulations to compare the changes in plasma methionine and homocysteine concentrations between ZDF and normal rats, by multiple administrations of the methionine-rich diet of 1 mmol/kg, daily for 60 days. The levels of methionine and homocysteine were elevated approximately two- and three-fold, respectively, in ZDF rats, while there were no changes observed in the normal control rats. These results can be interpreted to mean that both methionine and homocysteine will accumulate in patients with T2DM, who regularly consume high-methionine foods.
Thomas Edward Fitch
Full Text Available We describe a novel, potent and selective orexin-2 (OX2/hypocretin-2 receptor antagonist with in vivo activity in an animal model predictive of antidepressant-like efficacy. N-biphenyl-2-yl-4-fluoro-N-(1H-imidazol-2-ylmethylbenzenesulfonamide HCl (LSN2424100 binds with high affinity to recombinant human OX2 receptors (Ki = 4.5 nM, and selectivity over OX1 receptors (Ki = 393 nM. LSN2424100 inhibited OXA-stimulated intracellular calcium release in HEK293 cells expressing human and rat OX2 receptors (Kb = 0.44 and 0.83 nM, respectively preferentially over cells expressing human and rat OX1 (Kb = 90 and 175 nM, respectively. LSN2424100 exhibits good exposure in Sprague-Dawley rats after IP, but not PO, administration of a 30 mg/kg dose (AUC0-6h = 1300 and 269 ng*hr/mL, respectively. After IP administration in rats and mice, LSN2424100 produces dose-dependent antidepressant-like activity in the delayed-reinforcement of low rate (DRL assay, a model predictive of antidepressant-like efficacy. Efficacy in the DRL model was lost in mice lacking OX2, but not OX1 receptors, confirming OX2-specific activity. Importantly, antidepressant-like efficacy of the tricyclic antidepressant, imipramine, was maintained in both OX1 and OX2 receptor knock-out mice. In conclusion, the novel OX2 receptor antagonist, LSN2424100, is a valuable tool compound that can be used to explore the role of OX2 receptor-mediated signaling in mood disorders.
Sounds in the natural environment need to be assigned to acoustic sources to evaluate complex auditory scenes. Separating sources will affect the analysis of auditory features of sounds. As the benefits of assigning sounds to specific sources accrue to all species communicating acoustically, the ability for auditory scene analysis is widespread among different animals. Animal studies allow for a deeper insight into the neuronal mechanisms underlying auditory scene analysis. Here, we will review the paradigms applied in the study of auditory scene analysis and streaming of sequential sounds in animal models. We will compare the psychophysical results from the animal studies to the evidence obtained in human psychophysics of auditory streaming, i.e. in a task commonly used for measuring the capability for auditory scene analysis. Furthermore, the neuronal correlates of auditory streaming will be reviewed in different animal models and the observations of the neurons’ response measures will be related to perception. The across-species comparison will reveal whether similar demands in the analysis of acoustic scenes have resulted in similar perceptual and neuronal processing mechanisms in the wide range of species being capable of auditory scene analysis. This article is part of the themed issue ‘Auditory and visual scene analysis’. PMID:28044022
Wu, Xiaoping; Lund, Mogens Sandø; Sun, Dongxiao
This study investigated reliability of genomic prediction in various scenarios with regard to relationship between test and reference animals and between animals within the reference population. Different reference populations were generated from EuroGenomics data and 1288 Nordic Holstein bulls...... as a common test population. A GBLUP model and a Bayesian mixture model were applied to predict Genomic breeding values for bulls in the test data. Result showed that a closer relationship between test and reference animals led to a higher reliability, while a closer relationship between reference animal...
Campo, M Saveria
Tumorigenesis due to papillomavirus (PV) infection was first demonstrated in rabbits and cattle early last century. Despite the evidence obtained in animals, the role of viruses in human cancer was dismissed as irrelevant. It took a paradigm shift in the late 1970s for some viruses to be recognised as 'tumour viruses' in humans, and in 1995, more than 60 years after Rous's first demonstration of CRPV oncogenicity, WHO officially declared that 'HPV-16 and HPV-18 are carcinogenic to humans'. Experimental studies with animal PVs have been a determining factor in this decision. Animal PVs have been studied both as agents of disease in animals and as models of human PV infection. In addition to the study of PV infection in whole animals, in vitro studies with animal PV proteins have contributed greatly to the understanding of the mechanisms of cell transformation. Animal PVs cause distressing diseases in both farm and companion animals, such as teat papillomatosis in cattle, equine sarcoids and canine oral papillomatosis and there is an urgent need to understand the pathogenesis of these problematic infections. Persistent and florid teat papillomatosis in cows can lead to mastitis, prevent the suckling of calves and make milking impossible; heavily affected animals are culled and so occasionally are whole herds. Equine sarcoids are often recurrent and untreatable and lead to loss of valuable animals. Canine oral papillomatosis can be very extensive and persistent and lead to great distress. Thus the continuing research in the biology of animal PVs is amply justified. BPVs and CRPV have been for many years the model systems with which to study the biology of HPV. Induction of papillomas and their neoplastic progression has been experimentally demonstrated and reproduced in cattle and rabbits, and virus-cofactor interactions have been elucidated in these systems. With the advancements in molecular and cell culture techniques, the direct study of HPV has become less
Bradley, Michael P; Nagamine, Claude M
Zika virus has garnered great attention over the last several years, as outbreaks of the disease have emerged throughout the Western Hemisphere. Until quite recently Zika virus was considered a fairly benign virus, with limited clinical severity in both people and animals. The size and scope of the outbreak in the Western Hemisphere has allowed for the identification of severe clinical disease that is associated with Zika virus infection, most notably microcephaly among newborns, and an association with Guillian–Barré syndrome in adults. This recent association with severe clinical disease, of which further analysis strongly suggested causation by Zika virus, has resulted in a massive increase in the amount of both basic and applied research of this virus. Both small and large animal models are being used to uncover the pathogenesis of this emerging disease and to develop vaccine and therapeutic strategies. Here we review the animal-model–based Zika virus research that has been performed to date. PMID:28662753
Dei-Cas, E.; Brun-Pascaud, M.; Bille-Hansen, Vivi
As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research. The parasite was reported in numerous mammals but P. carinii pneumonia (PCP) experimental models were...... the host immune response as well as Pneumocystis-surfactant interactions. Pigs and horses also develop spontaneous PCP. Treated with corticosteroids, piglets develop extensive PCP and could be used as a non-rodent model. Pneumocystis was detected in many non-human primates. Primates could represent...... a source of parasites taxonomically related to P. carinii sp. f hominis. Moreover, primates might be used as experimental hosts to human Pneumocystis. A marked variability of parasite levels among corticosteroid-treated animals and the fact that the origin of the parasite strain remains unknown...
Langrock, Roland; Hopcraft, J. Grant C.; Blackwell, Paul G.
in non-ideal scenarios, we show that generally the estimation of models of this type is both feasible and ecologically informative. We illustrate the approach using real movement data from 11 reindeer (Rangifer tarandus). Results indicate a directional bias towards a group centroid for reindeer......Group dynamic movement is a fundamental aspect of many species' movements. The need to adequately model individuals' interactions with other group members has been recognised, particularly in order to differentiate the role of social forces in individual movement from environmental factors. However......, to date, practical statistical methods which can include group dynamics in animal movement models have been lacking. We consider a flexible modelling framework that distinguishes a group-level model, describing the movement of the group's centre, and an individual-level model, such that each individual...
Full Text Available Allergic diseases have great impact on the quality of life of both people and domestic animals. They are increasing in prevalence in both animals and humans, possibly due to the changed lifestyle conditions and the decreased exposure to beneficial microorganisms. Dogs, in particular, suffer from environmental skin allergies and develop a clinical presentation which is very similar to the one of children with eczema. Thus, dogs are a very useful species to improve our understanding on the mechanisms involved in people’s allergies and a natural model to study eczema. Animal models are frequently used to elucidate mechanisms of disease and to control for confounding factors which are present in studies with patients with spontaneously occurring disease and to test new therapies that can be beneficial in both species. It has been found that drugs useful in one species can also have benefits in other species highlighting the importance of a comprehensive understanding of diseases across species and the value of comparative studies. The purpose of the current article is to review allergic diseases across species and to focus on how these diseases compare to the counterpart in people.
Choi, Ehn-Kyoung; Park, Dongsun; Kim, Tae Kyun; Lee, Sun Hee; Bae, Dae-Kwon; Yang, Goeun; Yang, Yun-Hui; Kyung, Jangbeen; Kim, Dajeong; Lee, Woo Ryoung; Suh, Jun-Gyo; Jeong, Eun-Suk; Kim, Seung U.
Periventricular leukomalacia, specifically characterized as white matter injury, in neonates is strongly associated with the damage of pre-myelinating oligodendrocytes. Clinical data suggest that hypoxia-ischemia during delivery and intrauterine or neonatal infection-inflammation are important factors in the etiology of periventricular leukomalacia including cerebral palsy, a serious case exhibiting neurobehavioral deficits of periventricular leukomalacia. In order to explore the pathophysiological mechanisms of white matter injury and to better understand how infectious agents may affect the vulnerability of the immature brain to injury, novel animal models have been developed using hypoperfusion, microbes or bacterial products (lipopolysaccharide) and excitotoxins. Such efforts have developed rat models that produce predominantly white matter lesions by adopting combined hypoxia-ischemia technique on postnatal days 1-7, in which unilateral or bilateral carotid arteries of animals are occluded (ischemia) followed by 1-2 hour exposure to 6-8% oxygen environment (hypoxia). Furthermore, low doses of lipopolysaccharide that by themselves have no adverse-effects in 7-day-old rats, dramatically increase brain injury to hypoxic-ischemic challenge, implying that inflammation sensitizes the immature central nervous system. Therefore, among numerous models of periventricular leukomalacia, combination of hypoxia-ischemia-lipopolysaccharide might be one of the most-acceptable rodent models to induce extensive white matter injury and ensuing neurobehavioral deficits for the evaluation of candidate therapeutics. PMID:21826166
Allen, Richard P; Donelson, Nathan C; Jones, Byron C; Li, Yuqing; Manconi, Mauro; Rye, David B; Sanyal, Subhabrata; Winkelmann, Juliane
Restless legs syndrome (RLS) is a complex disorder that involves sensory and motor systems. The major pathophysiology of RLS is low iron concentration in the substantia nigra containing the cell bodies of dopamine neurons that project to the striatum, an area that is crucial for modulating movement. People who have RLS often present with normal iron values outside the brain; recent studies implicate several genes are involved in the syndrome. Like most complex diseases, animal models usually do not faithfully capture the full phenotypic spectrum of "disease," which is a uniquely human construct. Nonetheless, animal models have proven useful in helping to unravel the complex pathophysiology of diseases such as RLS and suggesting novel treatment paradigms. For example, hypothesis-independent genome-wide association studies (GWAS) have identified several genes as increasing the risk for RLS, including BTBD9. Independently, the murine homolog Btbd9 was identified as a candidate gene for iron regulation in the midbrain in mice. The relevance of the phenotype of another of the GWAS identified genes, MEIS1, has also been explored. The role of Btbd9 in iron regulation and RLS-like behaviors has been further evaluated in mice carrying a null mutation of the gene and in fruit flies when the BTBD9 protein is degraded. The BTBD9 and MEIS1 stories originate from human GWAS research, supported by work in a genetic reference population of mice (forward genetics) and further verified in mice, fish flies, and worms. Finally, the role of genetics is further supported by an inbred mouse strain that displays many of the phenotypic characteristics of RLS. The role of animal models of RLS phenotypes is also extended to include periodic limb movements. Copyright © 2016 Elsevier B.V. All rights reserved.
Full Text Available Abstract Background The concept of conserved processes presents unique opportunities for using nonhuman animal models in biomedical research. However, the concept must be examined in the context that humans and nonhuman animals are evolved, complex, adaptive systems. Given that nonhuman animals are examples of living systems that are differently complex from humans, what does the existence of a conserved gene or process imply for inter-species extrapolation? Methods We surveyed the literature including philosophy of science, biological complexity, conserved processes, evolutionary biology, comparative medicine, anti-neoplastic agents, inhalational anesthetics, and drug development journals in order to determine the value of nonhuman animal models when studying conserved processes. Results Evolution through natural selection has employed components and processes both to produce the same outcomes among species but also to generate different functions and traits. Many genes and processes are conserved, but new combinations of these processes or different regulation of the genes involved in these processes have resulted in unique organisms. Further, there is a hierarchy of organization in complex living systems. At some levels, the components are simple systems that can be analyzed by mathematics or the physical sciences, while at other levels the system cannot be fully analyzed by reducing it to a physical system. The study of complex living systems must alternate between focusing on the parts and examining the intact whole organism while taking into account the connections between the two. Systems biology aims for this holism. We examined the actions of inhalational anesthetic agents and anti-neoplastic agents in order to address what the characteristics of complex living systems imply for inter-species extrapolation of traits and responses related to conserved processes. Conclusion We conclude that even the presence of conserved processes is
Greek, Ray; Rice, Mark J
The concept of conserved processes presents unique opportunities for using nonhuman animal models in biomedical research. However, the concept must be examined in the context that humans and nonhuman animals are evolved, complex, adaptive systems. Given that nonhuman animals are examples of living systems that are differently complex from humans, what does the existence of a conserved gene or process imply for inter-species extrapolation? We surveyed the literature including philosophy of science, biological complexity, conserved processes, evolutionary biology, comparative medicine, anti-neoplastic agents, inhalational anesthetics, and drug development journals in order to determine the value of nonhuman animal models when studying conserved processes. Evolution through natural selection has employed components and processes both to produce the same outcomes among species but also to generate different functions and traits. Many genes and processes are conserved, but new combinations of these processes or different regulation of the genes involved in these processes have resulted in unique organisms. Further, there is a hierarchy of organization in complex living systems. At some levels, the components are simple systems that can be analyzed by mathematics or the physical sciences, while at other levels the system cannot be fully analyzed by reducing it to a physical system. The study of complex living systems must alternate between focusing on the parts and examining the intact whole organism while taking into account the connections between the two. Systems biology aims for this holism. We examined the actions of inhalational anesthetic agents and anti-neoplastic agents in order to address what the characteristics of complex living systems imply for inter-species extrapolation of traits and responses related to conserved processes. We conclude that even the presence of conserved processes is insufficient for inter-species extrapolation when the trait or response
Imanishi, Yasuo; Nagata, Yuki; Inaba, Masaaki
CIRCULATING CALCIUM AND PHOSPHATE ARE TIGHTLY REGULATED BY THREE HORMONES: the active form of vitamin D (1,25-dihydroxyvitamin D), fibroblast growth factor (FGF)-23, and parathyroid hormone (PTH). PTH acts to stimulate a rapid increment in serum calcium and has a crucial role in calcium homeostasis. Major target organs of PTH are kidney and bone. The oversecretion of the hormone results in hypercalcemia, caused by increased intestinal calcium absorption, reduced renal calcium clearance, and mobilization of calcium from bone in primary hyperparathyroidism. In chronic kidney disease, secondary hyperparathyroidism of uremia is observed in its early stages, and this finally develops into the autonomous secretion of PTH during maintenance hemodialysis. Receptors in parathyroid cells, such as the calcium-sensing receptor, vitamin D receptor, and FGF receptor (FGFR)-Klotho complex have crucial roles in the regulation of PTH secretion. Genes such as Cyclin D1, RET, MEN1, HRPT2, and CDKN1B have been identified in parathyroid diseases. Genetically engineered animals with these receptors and the associated genes have provided us with valuable information on the patho-physiology of parathyroid diseases. The application of these animal models is significant for the development of new therapies.
Full Text Available Circulating calcium and phosphate are tightly regulated by 3 hormones: the active form of vitamin D (1,25-dihydroxyvitamin D, fibroblast growth factor (FGF-23, and parathyroid hormone (PTH. PTH acts to stimulate a rapid increment in serum calcium and has a crucial role in calcium homeostasis. Major target organs of PTH are kidney and bone. The oversecretion of the hormone results in hypercalcemia, caused by increased intestinal calcium absorption, reduced renal calcium clearance, and mobilization of calcium from bone in primary hyperparathyroidism. In chronic kidney disease, secondary hyperparathyroidism of uremia is observed in its early stages, and early stages, and this finally develops into the autonomous secretion of PTH during maintenance hemodialysis. Receptors in parathyroid cells, such as the calcium-sensing receptor, vitamin D receptor, and FGF receptor (FGFR-Klotho complex have crucial roles in the regulation of PTH secretion. Genes such as Cyclin D1, RET, MEN1, HRPT2, and CDKN1B have been identified in parathyroid diseases. Genetically engineered animals with these receptors and the associated genes have provided us with valuable information on the patho-physiology of parathyroid diseases. The application of these animal models is significant for the development of new therapies.
Ballarò, Riccardo; Costelli, Paola; Penna, Fabio
Cancer cachexia is a frequent syndrome that affects patient quality of life, anticancer treatment effectiveness, and overall survival. The lack of anticancer cachexia therapies likely relies on the complexity of the syndrome that renders difficult to design appropriate clinical trials and, conversely, on the insufficient knowledge of the underlying pathogenetic mechanisms. The aim of this review is to collect the most relevant latest information regarding cancer cachexia with a special focus on the experimental systems adopted for modeling the disease in translational studies. The scenario of preclinical models for the study of cancer cachexia is not static and is rapidly evolving in parallel with new prospective treatment options. The well established syngeneic models using rodent cancer cells injected ectopically are now used alongside new ones featuring orthotopic injection, human cancer cell or patient-derived xenograft, or spontaneous tumors in genetically engineered mice. The use of more complex animal models that better resemble cancer cachexia, ideally including also the administration of chemotherapy, will expand the understanding of the underlying mechanisms and will allow a more reliable evaluation of prospective drugs for translational purposes.
Veazey, Ronald S
Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates. Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials. Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.
refining formal, inductive predictive models is the quality of the archaeological and environmental data. To build models efficiently, relevant...geomorphology, and historic information . Lessons Learned: The original model was focused on the identification of prehistoric resources. This...system but uses predictive modeling informally . For example, there is no probability for buried archaeological deposits on the Burton Mesa, but there is
Osorio, Joseph A; Scheer, Justin K; Ames, Christopher P
Predictive analytic algorithms are designed to identify patterns in the data that allow for accurate predictions without the need for a hypothesis. Therefore, predictive modeling can provide detailed and patient-specific information that can be readily applied when discussing the risks of surgery with a patient. There are few studies using predictive modeling techniques in the adult spine surgery literature. These types of studies represent the beginning of the use of predictive analytics in spine surgery outcomes. We will discuss the advancements in the field of spine surgery with respect to predictive analytics, the controversies surrounding the technique, and the future directions.
Rosenwasser, Alan M
Clinical and epidemiological observations have revealed that alcohol abuse and alcoholism are associated with widespread disruptions in sleep and other circadian biological rhythms. As with other psychiatric disorders, animal models have been very useful in efforts to better understand the cause and effect relationships underlying the largely correlative human data. This review summarizes the experimental findings indicating bidirectional interactions between alcohol (ethanol) consumption and the circadian timing system, emphasizing behavioral studies conducted in the author's laboratory. Together with convergent evidence from multiple laboratories, the work summarized here establishes that ethanol intake (or administration) alters fundamental properties of the underlying circadian pacemaker. In turn, circadian disruption induced by either environmental or genetic manipulations can alter voluntary ethanol intake. These reciprocal interactions may create a vicious cycle that contributes to the downward spiral of alcohol and drug addiction. In the future, such studies may lead to the development of chronobiologically based interventions to prevent relapse and effectively mitigate some of the societal burden associated with such disorders. Copyright © 2015 Elsevier Inc. All rights reserved.
Greek, Ray; Menache, Andre
Systematic reviews are currently favored methods of evaluating research in order to reach conclusions regarding medical practice. The need for such reviews is necessitated by the fact that no research is perfect and experts are prone to bias. By combining many studies that fulfill specific criteria, one hopes that the strengths can be multiplied and thus reliable conclusions attained. Potential flaws in this process include the assumptions that underlie the research under examination. If the assumptions, or axioms, upon which the research studies are based, are untenable either scientifically or logically, then the results must be highly suspect regardless of the otherwise high quality of the studies or the systematic reviews. We outline recent criticisms of animal-based research, namely that animal models are failing to predict human responses. It is this failure that is purportedly being corrected via systematic reviews. We then examine the assumption that animal models can predict human outcomes to perturbations such as disease or drugs, even under the best of circumstances. We examine the use of animal models in light of empirical evidence comparing human outcomes to those from animal models, complexity theory, and evolutionary biology. We conclude that even if legitimate criticisms of animal models were addressed, through standardization of protocols and systematic reviews, the animal model would still fail as a predictive modality for human response to drugs and disease. Therefore, systematic reviews and meta-analyses of animal-based research are poor tools for attempting to reach conclusions regarding human interventions.
Han, Nayoung; Chae, Jung-woo; Jeon, Jihyun; Lee, Jaeyeon; Back, Hyun-moon; Song, Byungjeong; Kwon, Kwang-il; Kim, Sang Kyum; Yun, Hwi-yeol
Background Although alterations in the methionine metabolism cycle (MMC) have been associated with vascular complications of diabetes, there have not been consistent results about the levels of methionine and homocysteine in type 2 diabetes mellitus (T2DM). The aim of the current study was to predict changes in plasma methionine and homocysteine concentrations after simulated consumption of methionine-rich foods, following the development of a mathematical model for MMC in Zucker Diabetic Fat...
This report is the documentation for Task 7 of the Statewide Archaeological Predictive Model Set. The goal of this project is to : develop a set of statewide predictive models to assist the planning of transportation projects. PennDOT is developing t...
Levy, R.; Mcginness, H.
Investigations were performed to predict the power available from the wind at the Goldstone, California, antenna site complex. The background for power prediction was derived from a statistical evaluation of available wind speed data records at this location and at nearby locations similarly situated within the Mojave desert. In addition to a model for power prediction over relatively long periods of time, an interim simulation model that produces sample wind speeds is described. The interim model furnishes uncorrelated sample speeds at hourly intervals that reproduce the statistical wind distribution at Goldstone. A stochastic simulation model to provide speed samples representative of both the statistical speed distributions and correlations is also discussed.
Willeberg, Preben; Paisley, Larry; Lind, Peter
Epidemiological models have been used extensively as a tool in improving animal disease surveillance activities. A review of published papers identified three main groups of model applications: models for planning surveillance, models for evaluating the performance of surveillance systems...... and models for interpreting surveillance data as part of ongoing control or eradication programmes. Two Danish examples are outlined. The first illustrates how models were used in documenting country freedom from disease (trichinellosis) and the second demonstrates how models were of assistance in predicting...
Nielsen, Torben Skov; Madsen, Henrik; Nielsen, Henrik Aalborg
utilities as partners and users. The new models are evaluated for five wind farms in Denmark as well as one wind farm in Spain. It is shown that the predictions based on conditional parametric models are superior to the predictions obatined by state-of-the-art parametric models.......This paper briefly describes new models and methods for predicationg the wind power output from wind farms. The system is being developed in a project which has the research organization Risø and the department of Informatics and Mathematical Modelling (IMM) as the modelling team and all the Danish...
Singer, Alexander; Salman, Mo; Thulke, Hans-Hermann
Animal health is of societal importance as it affects human welfare, and anthropogenic interests shape decision making to assure animal health. Scientific advice to support decision making is manifold. Modelling, as one piece of the scientific toolbox, is appreciated for its ability to describe and structure data, to give insight in complex processes and to predict future outcome. In this paper we study the application of scientific modelling to support practical animal health decisions. We reviewed the 35 animal health related scientific opinions adopted by the Animal Health and Animal Welfare Panel of the European Food Safety Authority (EFSA). Thirteen of these documents were based on the application of models. The review took two viewpoints, the decision maker's need and the modeller's approach. In the reviewed material three types of modelling questions were addressed by four specific model types. The correspondence between tasks and models underpinned the importance of the modelling question in triggering the modelling approach. End point quantifications were the dominating request from decision makers, implying that prediction of risk is a major need. However, due to knowledge gaps corresponding modelling studies often shed away from providing exact numbers. Instead, comparative scenario analyses were performed, furthering the understanding of the decision problem and effects of alternative management options. In conclusion, the most adequate scientific support for decision making - including available modelling capacity - might be expected if the required advice is clearly stated. Copyright © 2011 Elsevier B.V. All rights reserved.
Olesen, Jes; Jansen-Olesen, Inger
The pharmaceutical industry shows a decreasing interest in the development of drugs for migraine. One of the reasons for this could be the lack of reliable animal models for studying the effect of acute and prophylactic migraine drugs. The infusion of glyceryl trinitrate (GTN) is the best validated...... and most studied human migraine model. Several attempts have been made to transfer this model to animals. The different variants of this model are discussed as well as other recent models....
Dahl Andersen, Maria; Alstrup, Aage Kristian Olsen; Duvald, Christina Søndergaard
Animal models remain essential to understand the fundamental mechanisms occurring in fetal medicine and obstetric diseases, such as intrauterine growth restriction, preeclampsia and gestational diabetes. These vary regarding the employed method used for induction of the disease, and vary regarding...... the animal characteristics (size, number of fetuses, placenta barrier type, etc). While none of these exactly mirrors the human condition, different pregnant animal models (mice, rats, guinea pigs, chinchillas, rabbits, sheep and pigs) are here described with respect to advantages and limitations...
Syracuse, Ellen Marie [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
The LANL Seismo-Acoustic team has a strong capability in developing data-driven models that accurately predict a variety of observations. These models range from the simple – one-dimensional models that are constrained by a single dataset and can be used for quick and efficient predictions – to the complex – multidimensional models that are constrained by several types of data and result in more accurate predictions. Team members typically build models of geophysical characteristics of Earth and source distributions at scales of 1 to 1000s of km, the techniques used are applicable for other types of physical characteristics at an even greater range of scales. The following cases provide a snapshot of some of the modeling work done by the Seismo- Acoustic team at LANL.
Weenink, Robert P.; Hollmann, Markus W.; van Hulst, Robert A.
Cerebral arterial gas embolism is a dreaded complication of diving and invasive medical procedures. Many different animal models have been used in research on cerebral arterial gas embolism. This review provides an overview of the most important characteristics of these animal models. The properties
Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan
Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. Copyright © 2016 the American Physiological Society.
Zhan, Xianbao; Wang, Fan; Bi, Yan
Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. PMID:27418683
Animal models are formidable tools to investigate the etiology, the course and the potential treatment of an illness. No convincing animal model of suicide has been produced to date, and despite the intensive study of thousands of animal species naturalists have not identified suicide in nonhuman species in field situations. When modeling suicidal behavior in the animal, the greatest challenge is reproducing the role of will and intention in suicide mechanics. To overcome this limitation, current investigations on animals focus on every single step leading to suicide in humans. The most promising endophenotypes worth investigating in animals are the cortisol social-stress response and the aggression/impulsivity trait, involving the serotonergic system. Astroglia, neurotrophic factors and neurotrophins are implied in suicide, too. The prevention of suicide rests on the identification and treatment of every element increasing the risk. Copyright © 2011 Elsevier Inc. All rights reserved.
Jansen-Olesen, Inger; Tfelt-Hansen, Peer; Olesen, Jes
responses are likely to be behavioral, allowing multiple experiments in each individual animal. Distinction is made between acute and prophylactic models and how to validate each of them. Modern insight into neurobiological mechanisms of migraine is so good that it is only a question of resources...... for headache has almost come to a standstill partly because of a lack of valid animal models. Here we review previous models with emphasis on optimal characteristics of a future model. In addition to selection of animal species, the method of induction of migraine-like changes and the method of recording...
Lutz, Thomas A.; Woods, Stephen C.
This is a review of animal models of obesity currently used in research. We have focused upon more commonly utilized models since there are far too many newly created models to consider, especially those caused by selective molecular genetic approaches modifying one or more genes in specific populations of cells. Further, we will not discuss the generation and use of inducible transgenic animals (induced knock-out or knock-in) even though they often bear significant advantages compared to traditional transgenic animals; influences of the genetic modification during the development of the animals can be minimized. The number of these animal models is simply too large to be covered in this chapter. PMID:22948848
Los Campos, De G.; Hickey, J.M.; Pong-Wong, R.; Daetwyler, H.D.; Calus, M.P.L.
Genomic-enabled prediction is becoming increasingly important in animal and plant breeding, and is also receiving attention in human genetics. Deriving accurate predictions of complex traits requires implementing whole-genome regression (WGR) models where phenotypes are regressed on thousands of
lambs to mineral supplements can be used to predict risks of deficiency will be demonstrated. In both cases ... Presented at the Symposium on 'Mineral Nutrition' at the 26th Annual Congress of the South African Society of Animal. Production, Pretoria, 6 ... aphosphorosis on veld pastures demonstrated just how much can be ...
Kleinert, Maximilian; Clemmensen, Christoffer; Hofmann, Susanna M
More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover...... available animal models of obesity and diabetes and highlight the advantages, limitations and important caveats of each of these models....
Full Text Available Middle ear acquired cholesteatoma is a pathological condition associated with otitis media, which may be associated with temporal bone resorption, otorrhea and hearing loss, and occasionally various other complications. Cholesteatoma is characterized by the enhanced proliferation of epithelial cells with aberrant morphologic characteristics. Unfortunately, our understanding of the mechanism underlying its pathogenesis is limited. To investigate its pathogenesis, different animal models have been used. This paper provides a brief overview of the current status of research in the field of pathogenesis of middle ear acquired cholesteatoma, four types of animal models previously reported on, up-to-date cholesteatoma research using these animal models, our current studies of the local hybrid ear model, and the future prospect of new animal models of middle ear cholesteatoma.
Capilla, Javier; Clemons, Karl V; Stevens, David A
Animal models of fungal infections are, and will remain, a key tool in the advancement of the medical mycology. Many different types of animal models of fungal infection have been developed, with murine models the most frequently used, for studies of pathogenesis, virulence, immunology, diagnosis, and therapy. The ability to control numerous variables in performing the model allows us to mimic human disease states and quantitatively monitor the course of the disease. However, no single model can answer all questions and different animal species or different routes of infection can show somewhat different results. Thus, the choice of which animal model to use must be made carefully, addressing issues of the type of human disease to mimic, the parameters to follow and collection of the appropriate data to answer those questions being asked. This review addresses a variety of uses for animal models in medical mycology. It focuses on the most clinically important diseases affecting humans and cites various examples of the different types of studies that have been performed. Overall, animal models of fungal infection will continue to be valuable tools in addressing questions concerning fungal infections and contribute to our deeper understanding of how these infections occur, progress and can be controlled and eliminated.
Helton, William S
There is a continuing debate in the psychological literature between researchers who lean more toward learning theories of expertise development and those who lean more toward talent theories. However, the development of human expertise has not been open to direct experimental methods and will probably continue to elude experimentalists in the future. A promising alternative to direct experimental methods is to use human animal models, a possibility that researchers in expertise seem to have overlooked. However, there are studies in the animal behavior literature that address the development of nonhuman animal expertise without specifically referring to the topic as expertise. In the present study, the author discusses two nonhuman animal examples of expertise development that have been researched by ethologists. Nonhuman animal expertise development, unlike human expertise development, is subject to direct experimentation. The author thus recommends that researchers use nonhuman animals in their studies of expertise.
In an effort to ensure chemical safety in light of regulatory advances away from reliance on animal testing, USEPA and L’Oréal have collaborated to develop a quantitative systemic toxicity prediction model. Prediction of human systemic toxicity has proved difficult and remains a ...
Sangild, Per T; Shen, René Liang; Pontoppidan, Peter Erik Lotko
of CIM, and how to prevent it. Animal models allow highly controlled experimental conditions, detailed organ (e.g. GIT) insights, standardized, clinically-relevant treatment regimens and discovery of new biomarkers. Still, surprisingly few results from animal models have been translated into clinical CIM......Chemotherapy for cancer patients induces damaging tissue reactions along the epithelium of the gastrointestinal tract (GIT). This chemotherapy-induced mucositis (CIM) is a serious side effect of cytotoxic drugs and several animal models of CIM have been developed to help understand the progression...... mangement and treatments. The results obtained from specific animal models can be difficult to translate to the diverse range of CIM manifestations in patients that vary according to the antineoplastic drugs, dose, underlying (cancer) disease and patient characteristics (e.g. age, genetics, body...
Berg, W.B. van den
Animal models of osteoarthritis (OA) provide valuable insight into pathogenetic pathways. Although OA is not an inflammatory disease, synovial activation clearly plays a role. Matrix metalloproteinases 3 (stromelysin) and 13 (collagenase) appear crucial, and a disintegrin and metalloproteinase with
This presentation will provide the evidence that ozone exposure in animal models induce neuroendocrine stress response and this stress response modulates lung injury and inflammation through adrenergic and glucocorticoid receptors.
Jäkel, Lieke; Van Nostrand, William E; Nicoll, James A R; Werring, David J; Verbeek, Marcel M
Cerebral amyloid angiopathy (CAA), due to vascular amyloid β (Aβ) deposition, is a risk factor for intracerebral haemorrhage and dementia. CAA can occur in sporadic or rare hereditary forms, and is almost invariably associated with Alzheimer's disease (AD). Experimental (animal) models are of great interest in studying mechanisms and potential treatments for CAA. Naturally occurring animal models of CAA exist, including cats, dogs and non-human primates, which can be used for longitudinal studies. However, due to ethical considerations and low throughput of these models, other animal models are more favourable for research. In the past two decades, a variety of transgenic mouse models expressing the human Aβ precursor protein (APP) has been developed. Many of these mouse models develop CAA in addition to senile plaques, whereas some of these models were generated specifically to study CAA. In addition, other animal models make use of a second stimulus, such as hypoperfusion or hyperhomocysteinemia (HHcy), to accelerate CAA. In this manuscript, we provide a comprehensive review of existing animal models for CAA, which can aid in understanding the pathophysiology of CAA and explore the response to potential therapies. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
Sidney D'MELLO, Stan FRANKLIN
Full Text Available Although it is a relatively new field of study, the animal cognition literature is quite extensive and difficult to synthesize. This paper explores the contributions a comprehensive, computational, cognitive model can make toward organizing and assimilating this literature, as well as toward identifying important concepts and their interrelations. Using the LIDA model as an example, a framework is described within which to integrate the diverse research in animal cognition. Such a framework can provide both an ontology of concepts and their relations, and a working model of an animal’s cognitive processes that can compliment active empirical research. In addition to helping to account for a broad range of cognitive processes, such a model can help to comparatively assess the cognitive capabilities of different animal species. After deriving an ontology for animal cognition from the LIDA model, we apply it to develop the beginnings of a database that maps the cognitive facilities of a variety of animal species. We conclude by discussing future avenues of research, particularly the use of computational models of animal cognition as valuable tools for hypotheses generation and testing [Current Zoology 57 (4: 499–513, 2011].
Daunton, Nancy G.
Practical information on candidate animal models for motion sickness research and on methods used to elicit and detect motion sickness in these models is provided. Four good potential models for use in motion sickness experiments include the dog, cat, squirrel monkey, and rat. It is concluded that the appropriate use of the animal models, combined with exploitation of state-of-the-art biomedical techniques, should generate a great step forward in the understanding of motion sickness mechanisms and in the development of efficient and effective approaches to its prevention and treatment in humans.
Earl, Julia E; Zollner, Patrick A
Connections between ecosystems via animals (active subsidies) support ecosystem services and contribute to numerous ecological effects. Thus, the ability to predict the spatial distribution of active subsidies would be useful for ecology and conservation. Previous work modelling active subsidies focused on implicit space or static distributions, which treat passive and active subsidies similarly. Active subsidies are fundamentally different from passive subsidies, because animals can respond to the process of subsidy deposition and ecosystem changes caused by subsidy deposition. We propose addressing this disparity by integrating animal movement and ecosystem ecology to advance active subsidy investigations, make more accurate predictions of subsidy spatial distributions, and enable a mechanistic understanding of subsidy spatial distributions. We review selected quantitative techniques that could be used to accomplish integration and lead to novel insights. The ultimate objective for these types of studies is predictions of subsidy spatial distributions from characteristics of the subsidy and the movement strategy employed by animals that transport subsidies. These advances will be critical in informing the management of ecosystem services, species conservation and ecosystem degradation related to active subsidies. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.
Sibonga, Jean D.
This slide presentation reviews the use of animal models to research and inform bone morphology, in particular relating to human research in bone loss as a result of low gravity environments. Reasons for use of animal models as tools for human research programs include: time-efficient, cost-effective, invasive measures, and predictability as some model are predictive for drug effects.
Bonde, Marianne; Botreau, R; Bracke, MBM
One major objective of Welfare Quality® is to propose harmonized methods for the overall assessment of animal welfare on farm and at slaughter that are science based and meet societal concerns. Welfare is a multidimensional concept and its assessment requires measures of different aspects. Welfare...... Quality® proposes a formal evaluation model whereby the data on animals or their environment are transformed into value scores that reflect compliance with 12 subcriteria and 4 criteria of good welfare. Each animal unit is then allocated to one of four categories: excellent welfare, enhanced welfare......, acceptable welfare and not classified. This evaluation model is tuned according to the views of experts from animal and social sciences, and stakeholders....
Nalberczak, Maria; Radwanska, Kasia
Our understanding of the neuronal and molecular basis of alcohol addiction is still not satisfactory. As a consequence we still miss successful therapy of alcoholism. One of the reasons for such state is the lack of appropriate animal models which would allow in-depth analysis of biological basis of addiction. Here we will present our efforts to create the animal model of alcohol addiction in the automated learning device, the IntelliCage setup. Applying this model to optogenetically modified mice with remotely controlled regulation of selected neuronal populations by light may lead to very precise identification of neuronal circuits involved in coding addiction-related behaviors.
Daniel, Sam J; Akinpelu, Olubunmi V; Sahmkow, Sofia; Funnell, W Robert J; Akache, Fadi
To investigate possible ototoxic effects of a one-time application of oxymetazoline drops in a chinchilla animal model with tympanostomy tubes. Study Design. A prospective, controlled animal study. The Research Institute of the Montreal's Children Hospital, McGill University Health Centre. Ventilation tubes were inserted in both ears of 12 animals. One ear was randomly assigned to receive oxymetazoline drops (0.5 mL). The contralateral ear did not receive any drops, serving as a control ear. Distortion product otoacoustic emissions were measured bilaterally for a wide range of frequencies (between 1 and 16 kHz) before and 1 day after the application of oxymetazoline in the experimental ears. Two months later, the animals were sacrificed and all cochleae were dissected out and processed for scanning electron microscopy. In this established chinchilla animal model, the measured distortion product otoacoustic emission amplitudes and the morphological appearance on scanning electron microscopy were similar for both control and experimental ears. Oxymetazoline did not cause ototoxicity in a chinchilla animal model 2 months after a single application via a tympanostomy tube.
McCarthy, F P
Preeclampsia remains a leading cause of maternal and fetal morbidity and mortality and has an unknown etiology. The limited progress made regarding new treatments to reduce the incidence and severity of preeclampsia has been attributed to the difficulties faced in the development of suitable animal models for the mechanistic research of this disease. In addition, animal models need hypotheses on which to be based and the slow development of testable hypotheses has also contributed to this poor progress. The past decade has seen significant advances in our understanding of preeclampsia and the development of viable reproducible animal models has contributed significantly to these advances. Although many of these models have features of preeclampsia, they are still poor overall models of the human disease and limited due to lack of reproducibility and because they do not include the complete spectrum of pathophysiological changes associated with preeclampsia. This review aims to provide a succinct and comprehensive assessment of current animal models of preeclampsia, their uses and limitations with particular attention paid to the best validated and most comprehensive models, in addition to those models which have been utilized to investigate potential therapeutic interventions for the treatment or prevention of preeclampsia.
Ben Bruno Policicchio
Full Text Available The HIV-1/AIDS pandemic continues to spread unabated worldwide and no vaccine exists within our grasp. Effective antiretroviral therapy (ART has been developed, but ART cannot clear the virus from the infected patient. A cure for HIV-1 is badly needed to stop both the spread of the virus in human populations and disease progression in infected individuals. A safe and effective cure strategy for HIV infection will require multiple tools and appropriate animal models are tools that are central to cure research. An ideal animal model should recapitulate the essential aspects of HIV pathogenesis and associated immune responses, while permitting invasive studies, thus allowing a thorough evaluation of strategies aimed at reducing the size of the reservoir (functional cure or eliminating the reservoir altogether (sterilizing cure. Since there is no perfect animal model for cure research, multiple models have been tailored and tested to address specific quintessential questions of virus persistence and eradication. The development of new nonhuman primate and mouse models, along with a certain interest in the feline model, have the potential to fuel cure research. In this review, we highlight the major animal models currently utilized for cure research and the contributions of each model to this goal.
Policicchio, Benjamin B; Pandrea, Ivona; Apetrei, Cristian
The HIV-1/AIDS pandemic continues to spread unabated worldwide, and no vaccine exists within our grasp. Effective antiretroviral therapy (ART) has been developed, but ART cannot clear the virus from the infected patient. A cure for HIV-1 is badly needed to stop both the spread of the virus in human populations and disease progression in infected individuals. A safe and effective cure strategy for human immunodeficiency virus (HIV) infection will require multiple tools, and appropriate animal models are tools that are central to cure research. An ideal animal model should recapitulate the essential aspects of HIV pathogenesis and associated immune responses, while permitting invasive studies, thus allowing a thorough evaluation of strategies aimed at reducing the size of the reservoir (functional cure) or eliminating the reservoir altogether (sterilizing cure). Since there is no perfect animal model for cure research, multiple models have been tailored and tested to address specific quintessential questions of virus persistence and eradication. The development of new non-human primate and mouse models, along with a certain interest in the feline model, has the potential to fuel cure research. In this review, we highlight the major animal models currently utilized for cure research and the contributions of each model to this goal.
Harding, John; Roberts, R Michael; Mirochnitchenko, Oleg
The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for novel animal models to expand the range of current studies, most of which have been conducted in rodents. Extant models are providing important information but have limitations for a variety of disease categories and can have different size and physiology relative to humans. These differences can preclude the ability to reproduce the results of animal-based preclinical studies in human trials. Larger animal species, such as rabbits, dogs, pigs, sheep, goats, and non-human primates, are better predictors of responses in humans than are rodents, but in each case it will be necessary to choose the best model for a specific application. There is a wide spectrum of potential stem cell-based products that can be used for regenerative medicine, including embryonic and induced pluripotent stem cells, somatic stem cells, and differentiated cellular progeny. The state of knowledge and availability of these cells from large animals vary among species. In most cases, significant effort is required for establishing and characterizing cell lines, comparing behavior to human analogs, and testing potential applications. Stem cell-based therapies present significant safety challenges, which cannot be addressed by traditional procedures and require the development of new protocols and test systems, for which the rigorous use of larger animal species more closely resembling human behavior will be required. In this article, we discuss the current status and challenges of and several major directions
Jung, Soo Yeon; Kim, Ha Yeong; Park, Hae Sang; Yin, Xiang Yun; Chung, Sung Min; Kim, Han Su
Ideal hypoparathyroidism animal models are a prerequisite to developing new treatment modalities for this disorder. The purpose of this study was to evaluate the feasibility of a model whereby rats were parathyroidectomized (PTX) using a fluorescent-identification method and the ideal calcium content of the diet was determined. Thirty male rats were divided into surgical sham (SHAM, n = 5) and PTX plus 0, 0.5, and 2% calcium diet groups (PTX-FC (n = 5), PTX-NC (n = 10), and PTX-HC (n = 10), respectively). Serum parathyroid hormone levels decreased to non-detectable levels in all PTX groups. All animals in the PTX-FC group died within 4 days after the operation. All animals survived when supplied calcium in the diet. However, serum calcium levels were higher in the PTX-HC than the SHAM group. The PTX-NC group demonstrated the most representative modeling of primary hypothyroidism. Serum calcium levels decreased and phosphorus levels increased, and bone volume was increased. All animals survived without further treatment and did not show nephrotoxicity including calcium deposits. These findings demonstrate that PTX animal models produced by using the fluorescent-identification method, and fed a 0.5% calcium diet, are appropriate for hypoparathyroidism treatment studies.
Soo Yeon Jung
Full Text Available Ideal hypoparathyroidism animal models are a prerequisite to developing new treatment modalities for this disorder. The purpose of this study was to evaluate the feasibility of a model whereby rats were parathyroidectomized (PTX using a fluorescent-identification method and the ideal calcium content of the diet was determined. Thirty male rats were divided into surgical sham (SHAM, n = 5 and PTX plus 0, 0.5, and 2% calcium diet groups (PTX-FC (n = 5, PTX-NC (n = 10, and PTX-HC (n = 10, respectively. Serum parathyroid hormone levels decreased to non-detectable levels in all PTX groups. All animals in the PTX-FC group died within 4 days after the operation. All animals survived when supplied calcium in the diet. However, serum calcium levels were higher in the PTX-HC than the SHAM group. The PTX-NC group demonstrated the most representative modeling of primary hypothyroidism. Serum calcium levels decreased and phosphorus levels increased, and bone volume was increased. All animals survived without further treatment and did not show nephrotoxicity including calcium deposits. These findings demonstrate that PTX animal models produced by using the fluorescent-identification method, and fed a 0.5% calcium diet, are appropriate for hypoparathyroidism treatment studies.
Park, Moo Kyun; Lee, Byung Don
Otitis media is defined as inflammation of the middle ear, including the auditory ossicles and the Eustachian tube. Otitis media is a major health problem in many societies. The causes of otitis media includes infection and anatomic/physiologic, host, and environmental factors. In general, otitis media is a childhood disease, and anatomic and physiologic changes have great effects on its development. Thus, in vitro or human experimental studies of otitis media are difficult. Several experimental animal models have been introduced to investigate the pathogenesis and treatment of otitis media. However, none are ideal. The aim of this review is to provide a brief overview of the current status of animal models of otitis media with effusion, acute otitis media, and cholesteatoma. This review will assist determination of the most appropriate animal models of otitis media.
Full Text Available Gaucher disease (GD, the most common lysosomal storage disorder (LSD, is caused by the defective activity of the lysosomal hydrolase glucocerebrosidase, which is encoded by the GBA gene. Generation of animal models that faithfully recapitulate the three clinical subtypes of GD has proved to be more of a challenge than first anticipated. The first mouse to be produced died within hours after birth owing to skin permeability problems, and mice with point mutations in Gba did not display symptoms correlating with human disease and also died soon after birth. Recently, conditional knockout mice that mimic some features of the human disease have become available. Here, we review the contribution of all currently available animal models to examining pathological pathways underlying GD and to testing the efficacy of new treatment modalities, and propose a number of criteria for the generation of more appropriate animal models of GD.
Full Text Available Marcelo Vivolo Aun,1,2 Rafael Bonamichi-Santos,1,2 Fernanda Magalhães Arantes-Costa,2 Jorge Kalil,1 Pedro Giavina-Bianchi1 1Clinical Immunology and Allergy Division, Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil, 2Laboratory of Experimental Therapeutics (LIM20, Department of Internal Medicine, University of Sao Paulo, Sao Paulo, Brazil Abstract: Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila, rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes
Sverjensky, Dimitri A. [Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Earth and Planetary Sciences
Surface complexation plays an important role in the equilibria and kinetics of processes controlling the compositions of soilwaters and groundwaters, the fate of contaminants in groundwaters, and the subsurface storage of CO2 and nuclear waste. Over the last several decades, many dozens of individual experimental studies have addressed aspects of surface complexation that have contributed to an increased understanding of its role in natural systems. However, there has been no previous attempt to develop a model of surface complexation that can be used to link all the experimental studies in order to place them on a predictive basis. Overall, my research has successfully integrated the results of the work of many experimentalists published over several decades. For the first time in studies of the geochemistry of the mineral-water interface, a practical predictive capability for modeling has become available. The predictive correlations developed in my research now enable extrapolations of experimental studies to provide estimates of surface chemistry for systems not yet studied experimentally and for natural and anthropogenically perturbed systems.
Samadi; Wajizah, S.; Munawar, A. A.
Feed plays an important factor in animal production. The purpose of this study is to apply NIRS method in determining feed values. NIRS spectra data were acquired for feed samples in wavelength range of 1000 - 2500 nm with 32 scans and 0.2 nm wavelength. Spectral data were corrected by de-trending (DT) and standard normal variate (SNV) methods. Prediction of in vitro dry matter digestibility (IVDMD) and in vitro organic matter digestibility (IVOMD) were established as model by using principal component regression (PCR) and validated using leave one out cross validation (LOOCV). Prediction performance was quantified using coefficient correlation (r) and residual predictive deviation (RPD) index. The results showed that IVDMD and IVOMD can be predicted by using SNV spectra data with r and RPD index: 0.93 and 2.78 for IVDMD ; 0.90 and 2.35 for IVOMD respectively. In conclusion, NIRS technique appears feasible to predict animal feed nutritive values.
Gerdts, Volker; Wilson, Heather L; Meurens, Francois; van Drunen Littel-van den Hurk, Sylvia; Wilson, Don; Walker, Stewart; Wheler, Colette; Townsend, Hugh; Potter, Andrew A
The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importantly, no single animal model provides all the information required for advancing a new vaccine through the preclinical stage, and research over the last two decades has highlighted that large animals more accurately predict vaccine outcome in humans than do other models. Here we review the advantages and disadvantages of large animal models for human vaccine development and demonstrate that much of the success in bringing a new vaccine to market depends on choosing the most appropriate animal model for preclinical testing. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: email@example.com.
Presents a simulation model which was developed to predict average daily gain in cattle and sheep grazing different species and swards of different species composition on Dohne Sourveld. The model was based upon measured ingestive and digestive characteristics of different grass species and incorporates an explicit ...
Kévin P. Dhondt
Full Text Available The Henipavirus genus contains two highly lethal viruses, the Hendra and Nipah viruses and one, recently discovered, apparently nonpathogenic member; Cedar virus. These three, negative-sense single-stranded RNA viruses, are hosted by fruit bats and use EphrinB2 receptors for entry into cells. The Hendra and Nipah viruses are zoonotic pathogens that emerged in the middle of 90s and have caused severe, and often fatal, neurologic and/or respiratory diseases in both humans and different animals; including spillover into equine and porcine species. Development of relevant models is critical for a better understanding of viral pathogenesis, generating new diagnostic tools, and assessing anti-viral therapeutics and vaccines. This review summarizes available data on several animal models where natural and/or experimental infection has been demonstrated; including pteroid bats, horses, pigs, cats, hamsters, guinea pigs, ferrets, and nonhuman primates. It recapitulates the principal features of viral pathogenesis in these animals and current knowledge on anti-viral immune responses. Lastly it describes the recently characterized murine animal model, which provides the possibility to use numerous and powerful tools available for mice to further decipher henipaviruses immunopathogenesis, prophylaxis, and treatment. The utility of different models to analyze important aspects of henipaviruses-induced disease in humans, potential routes of transmission, and therapeutic approaches are equally discussed.
Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas
This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking...
Pérez-Rial, Sandra; Girón-Martínez, Álvaro; Peces-Barba, Germán
Animal models of disease have always been welcomed by the scientific community because they provide an approach to the investigation of certain aspects of the disease in question. Animal models of COPD cannot reproduce the heterogeneity of the disease and usually only manage to represent the disease in its milder stages. Moreover, airflow obstruction, the variable that determines patient diagnosis, not always taken into account in the models. For this reason, models have focused on the development of emphysema, easily detectable by lung morphometry, and have disregarded other components of the disease, such as airway injury or associated vascular changes. Continuous, long-term exposure to cigarette smoke is considered the main risk factor for this disease, justifying the fact that the cigarette smoke exposure model is the most widely used. Some variations on this basic model, related to exposure time, the association of other inducers or inhibitors, exacerbations or the use of transgenic animals to facilitate the identification of pathogenic pathways have been developed. Some variations or heterogeneity of this disease, then, can be reproduced and models can be designed for resolving researchers' questions on disease identification or treatment responses. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.
Nielsen, Henrik Aalborg; Nielsen, Torben Skov; Madsen, Henrik
This document lists candidate prediction models for Work Package 3 (WP3) of the PSO-project called ``Intelligent wind power prediction systems'' (FU4101). The main focus is on the models transforming numerical weather predictions into predictions of power production. The document also outlines...
Full Text Available Due to the biological complexity of the cardiovascular system, the animal model is an urgent pre-clinical need to advance our knowledge of cardiovascular disease and to explore new drugs to repair the damaged heart. Ideally, a model system should be inexpensive, easily manipulated, reproducible, a biological representative of human disease, and ethically sound. Although a larger animal model is more expensive and difficult to manipulate, its genetic, structural, functional, and even disease similarities to humans make it an ideal model to first consider. This review presents the commonly-used large animals—dog, sheep, pig, and non-human primates—while the less-used other large animals—cows, horses—are excluded. The review attempts to introduce unique points for each species regarding its biological property, degrees of susceptibility to develop certain types of heart diseases, and methodology of induced conditions. For example, dogs barely develop myocardial infarction, while dilated cardiomyopathy is developed quite often. Based on the similarities of each species to the human, the model selection may first consider non-human primates—pig, sheep, then dog—but it also depends on other factors, for example, purposes, funding, ethics, and policy. We hope this review can serve as a basic outline of large animal models for cardiovascular researchers and clinicians.
Oleshko, A N; Kornienko, V V; Tkachenko, Yu A; Kurganskaya, V A
To assess the skin regeneration and explore new medical devices for the treatment of skin defects is necessary to conduct long-term experiments using laboratory animals. Currently, there are many methods for skin trauma modeling but most of them have disadvantages that limit their use. The purpose of this work - the development of an experimental model of the formation of skin defect of various etiologies with the specified parameters of depth and area of damage to the absence of systemic effects on the animal's body. We have developed an installation that allows us to form a skin defect of mechanical, thermal and chemical etiology with area from 1.76 cm2 to 2.0 cm2. The experiment was conducted on 18 male laboratory rats to examine the effectiveness of current method and control the depth and area of the defect. As a result of the new methodology, we were able to carry out simulation skin injuries of different etiology on laboratory animals in the short term and reduce the severity of injuries to extend the life span of animals to monitor the repair processes, as well as to standardize the modeling of injuries according to the criteria of area and depth of the defect.
Biessels, G J; Bril, V; Calcutt, N A
of statistically different values between diabetic and control animals in 2 of 3 assessments (nocifensive behavior, nerve conduction velocities, or nerve structure). The participants propose that this framework would allow different research groups to compare and share data, with an emphasis on data targeted......NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy....... The discussion was divided into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve structure, (3) electrophysiological assessments of nerve function, (4) behavioral assessments of nerve function, and (5) the role of biomarkers in disease phenotyping. Participants discussed the current...
Alline C. Campos
Full Text Available Anxiety and stress-related disorders are severe psychiatric conditions that affect performance in daily tasks and represent a high cost to public health. The initial observation of Charles Darwin that animals and human beings share similar characteristics in the expression of emotion raise the possibility of studying the mechanisms of psychiatric disorders in other mammals (mainly rodents. The development of animal models of anxiety and stress has helped to identify the pharmacological mechanisms and potential clinical effects of several drugs. Animal models of anxiety are based on conflict situations that can generate opposite motivational states induced by approach-avoidance situations. The present review revisited the main rodent models of anxiety and stress responses used worldwide. Here we defined as “ethological” the tests that assess unlearned/unpunished responses (such as the elevated plus maze, light-dark box, and open field, whereas models that involve learned/punished responses are referred to as “conditioned operant conflict tests” (such as the Vogel conflict test. We also discussed models that involve mainly classical conditioning tests (fear conditioning. Finally, we addressed the main protocols used to induce stress responses in rodents, including psychosocial (social defeat and neonatal isolation stress, physical (restraint stress, and chronic unpredictable stress.
Full Text Available Background/Aim. The lack of effective therapy for advanced stages of melanoma emphasizes the importance of preventive measures and screenings of population at risk. Identifying individuals at high risk should allow targeted screenings and follow-up involving those who would benefit most. The aim of this study was to identify most significant factors for melanoma prediction in our population and to create prognostic models for identification and differentiation of individuals at risk. Methods. This case-control study included 697 participants (341 patients and 356 controls that underwent extensive interview and skin examination in order to check risk factors for melanoma. Pairwise univariate statistical comparison was used for the coarse selection of the most significant risk factors. These factors were fed into logistic regression (LR and alternating decision trees (ADT prognostic models that were assessed for their usefulness in identification of patients at risk to develop melanoma. Validation of the LR model was done by Hosmer and Lemeshow test, whereas the ADT was validated by 10-fold cross-validation. The achieved sensitivity, specificity, accuracy and AUC for both models were calculated. The melanoma risk score (MRS based on the outcome of the LR model was presented. Results. The LR model showed that the following risk factors were associated with melanoma: sunbeds (OR = 4.018; 95% CI 1.724- 9.366 for those that sometimes used sunbeds, solar damage of the skin (OR = 8.274; 95% CI 2.661-25.730 for those with severe solar damage, hair color (OR = 3.222; 95% CI 1.984-5.231 for light brown/blond hair, the number of common naevi (over 100 naevi had OR = 3.57; 95% CI 1.427-8.931, the number of dysplastic naevi (from 1 to 10 dysplastic naevi OR was 2.672; 95% CI 1.572-4.540; for more than 10 naevi OR was 6.487; 95%; CI 1.993-21.119, Fitzpatricks phototype and the presence of congenital naevi. Red hair, phototype I and large congenital naevi were
Guidetti, Roberto; Baraldi, Laura; Calzolai, Caterina; Pini, Lorenza; Veronesi, Paola; Pederzoli, Aurora
Background Science curricula and teachers should emphasize evolution in a manner commensurate with its importance as a unifying concept in science. The concept of adaptation represents a first step to understand the results of natural selection. We settled an experimental project of alternative didactic to improve knowledge of organism adaptation. Students were involved and stimulated in learning processes by creative activities. To set adaptation in a historic frame, fossil records as evidence of past life and evolution were considered. Results The experimental project is schematized in nine phases: review of previous knowledge; lesson on fossils; lesson on fantastic animals; planning an imaginary world; creation of an imaginary animal; revision of the imaginary animals; adaptations of real animals; adaptations of fossil animals; and public exposition. A rubric to evaluate the student's performances is reported. The project involved professors and students of the University of Modena and Reggio Emilia and of the "G. Marconi" Secondary School of First Degree (Modena, Italy). Conclusion The educational objectives of the project are in line with the National Indications of the Italian Ministry of Public Instruction: knowledge of the characteristics of living beings, the meanings of the term "adaptation", the meaning of fossils, the definition of ecosystem, and the particularity of the different biomes. At the end of the project, students will be able to grasp particular adaptations of real organisms and to deduce information about the environment in which the organism evolved. This project allows students to review previous knowledge and to form their personalities. PMID:17767729
Kleinstreuer, Nicole C; Hoffmann, Sebastian; Alépée, Nathalie; Allen, David; Ashikaga, Takao; Casey, Warren; Clouet, Elodie; Cluzel, Magalie; Desprez, Bertrand; Gellatly, Nichola; Göbel, Carsten; Kern, Petra S; Klaric, Martina; Kühnl, Jochen; Martinozzi-Teissier, Silvia; Mewes, Karsten; Miyazawa, Masaaki; Strickland, Judy; van Vliet, Erwin; Zang, Qingda; Petersohn, Dirk
Skin sensitization is a toxicity endpoint of widespread concern, for which the mechanistic understanding and concurrent necessity for non-animal testing approaches have evolved to a critical juncture, with many available options for predicting sensitization without using animals. Cosmetics Europe and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods collaborated to analyze the performance of multiple non-animal data integration approaches for the skin sensitization safety assessment of cosmetics ingredients. The Cosmetics Europe Skin Tolerance Task Force (STTF) collected and generated data on 128 substances in multiple in vitro and in chemico skin sensitization assays selected based on a systematic assessment by the STTF. These assays, together with certain in silico predictions, are key components of various non-animal testing strategies that have been submitted to the Organization for Economic Cooperation and Development as case studies for skin sensitization. Curated murine local lymph node assay (LLNA) and human skin sensitization data were used to evaluate the performance of six defined approaches, comprising eight non-animal testing strategies, for both hazard and potency characterization. Defined approaches examined included consensus methods, artificial neural networks, support vector machine models, Bayesian networks, and decision trees, most of which were reproduced using open source software tools. Multiple non-animal testing strategies incorporating in vitro, in chemico, and in silico inputs demonstrated equivalent or superior performance to the LLNA when compared to both animal and human data for skin sensitization.
Full Text Available Rabies is a serious concern to public health and wildlife management worldwide. Over the last three decades, various mathematical models have been proposed to study the transmission dynamics of rabies. In this paper we provide a mini-review on some reaction-diffusion models describing the spatial spread of rabies among animals. More specifically, we introduce the susceptible-exposed-infectious models for the spatial transmission of rabies among foxes (Murray et al., 1986, the spatiotemporal epidemic model for rabies among raccoons (Neilan and Lenhart, 2011, the diffusive rabies model for skunk and bat interactions (Bonchering et al., 2012, and the reaction-diffusion model for rabies among dogs (Zhang et al., 2012. Numerical simulations on the spatiotemporal dynamics of these models from these papers are presented.
Wang, Sunan; Zhu, Fan
The ever-increasing occurrence of diabetes worldwide demands cost-effective anti-diabetic strategies. Food-based materials have great potential as efficient anti-diabetic agents. Focusing on the literatures of the recent 5years, this review summarizes the methods, findings, and limitations of each research involving non-medicinal foods (individual and mixed) and diabetic animal models. Various types of fruits, vegetables, legumes, cereals, spices, beverages, oilseeds, and edible oils showed antidiabetic effects in different animal models. Animal feeding trials rarely had identical designs in food doses, feeding schedules, and routes of administration, as well as biochemical markers for antidiabetic evaluation. Various possible cellular and metabolic targets were speculated for the anti-hyperglycemic effects of the dietary materials, and the molecular mechanisms of action remain to be better explored. Short-term (maximum 16weeks) antidiabetic studies have been established. Limited safety/tolerability data are available for antidiabetic dietary materials. Findings from current animal studies present a generic antidiabetic dietary pattern associated with plant-based whole foods, which agrees well with the findings of epidemiological studies. Copyright © 2016 Elsevier Ltd. All rights reserved.
Carter, Anthony Michael
This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however...... and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial...
Mege, Diane; Mezouar, Soraya; Dignat-George, Françoise; Panicot-Dubois, Laurence; Dubois, Christophe
Cancer-associated venous thromboembolism (VTE) constitutes the second cause of death after cancer. Many risk factors for cancer-associated VTE have been identified, among them soluble tissue factor and microparticles (MPs). Few data are available about the implication of MPs in cancer associated-VTE through animal model of cancer. The objective of the present review was to report the state of the current literature about MPs and cancer-associated VTE in animal model of cancer. Fourteen series have reported the role of MPs in cancer-associated VTE, through three main mouse models: ectopic or orthotopic tumor induction, experimental metastasis by intravenous injection of tumor cells into the lateral tail vein of the mouse. Pancreatic cancer is the most used animal model, due to its high rate of cancer-associated VTE. All the series reported that tumor cell-derived MPs can promote thrombus formation in TF-dependent manner. Some authors reported also the implication of phosphatidylserine and PSGL1 in the generation of thrombin. Moreover, MPs seem to be implicated in cancer progression through a coagulation-dependent mechanism secondary to thrombocytosis, or a mechanism implicating the regulation of the immune response. For these reasons, few authors have reported that antiplatelet and anticoagulant treatments may prevent tumor progression and the formation of metastases in addition of coagulopathy. © 2016 Elsevier Ltd. All rights reserved.
Full Text Available Research for a novel vaccine to prevent tuberculosis is an urgent medical need. The current vaccine, BCG, has demonstrated a non-homogenous efficacy in humans, but still is the gold standard to be improved upon. In general, the main indicator for testing the potency of new candidates in animal models is the reduction of the bacillary load in the lungs at the acute phase of the infection. Usually, this reduction is similar to that induced by BCG, although in some cases a weak but significant improvement can be detected, but none of candidates are able to prevent establishment of infection. The main characteristics of several laboratory animals are reviewed, reflecting that none are able to simulate the whole characteristics of human tuberculosis. As, so far, no surrogate of protection has been found, it is important to test new candidates in several models in order to generate convincing evidence of efficacy that might be better than that of BCG in humans. It is also important to investigate the use of “in silico” and “ex vivo” models to better understand experimental data and also to try to replace, or at least reduce and refine experimental models in animals.
Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.
Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444
Torres, Arnau; Gómez, Javier
The computational modelling of deformations has been actively studied for the last thirty years. This is mainly due to its large range of applications that include computer animation, medical imaging, shape estimation, face deformation as well as other parts of the human body, and object tracking. In addition, these advances have been supported by the evolution of computer processing capabilities, enabling realism in a more sophisticated way. This book encompasses relevant works of expert researchers in the field of deformation models and their applications. The book is divided into two main parts. The first part presents recent object deformation techniques from the point of view of computer graphics and computer animation. The second part of this book presents six works that study deformations from a computer vision point of view with a common characteristic: deformations are applied in real world applications. The primary audience for this work are researchers from different multidisciplinary fields, s...
Lopes, F B; Wu, X-L; Li, H; Xu, J; Perkins, T; Genho, J; Ferretti, R; Tait, R G; Bauck, S; Rosa, G J M
Reliable genomic prediction of breeding values for quantitative traits requires the availability of sufficient number of animals with genotypes and phenotypes in the training set. As of 31 October 2016, there were 3,797 Brangus animals with genotypes and phenotypes. These Brangus animals were genotyped using different commercial SNP chips. Of them, the largest group consisted of 1,535 animals genotyped by the GGP-LDV4 SNP chip. The remaining 2,262 genotypes were imputed to the SNP content of the GGP-LDV4 chip, so that the number of animals available for training the genomic prediction models was more than doubled. The present study showed that the pooling of animals with both original or imputed 40K SNP genotypes substantially increased genomic prediction accuracies on the ten traits. By supplementing imputed genotypes, the relative gains in genomic prediction accuracies on estimated breeding values (EBV) were from 12.60% to 31.27%, and the relative gain in genomic prediction accuracies on de-regressed EBV was slightly small (i.e. 0.87%-18.75%). The present study also compared the performance of five genomic prediction models and two cross-validation methods. The five genomic models predicted EBV and de-regressed EBV of the ten traits similarly well. Of the two cross-validation methods, leave-one-out cross-validation maximized the number of animals at the stage of training for genomic prediction. Genomic prediction accuracy (GPA) on the ten quantitative traits was validated in 1,106 newly genotyped Brangus animals based on the SNP effects estimated in the previous set of 3,797 Brangus animals, and they were slightly lower than GPA in the original data. The present study was the first to leverage currently available genotype and phenotype resources in order to harness genomic prediction in Brangus beef cattle. © 2018 Blackwell Verlag GmbH.
Di Segni, Matteo; Patrono, Enrico; Patella, Loris; Puglisi-Allegra, Stefano; Ventura, Rossella
Eating disorders are multifactorial conditions that can involve a combination of genetic, metabolic, environmental, and behavioral factors. Studies in humans and laboratory animals show that eating can also be regulated by factors unrelated to metabolic control. Several studies suggest a link between stress, access to highly palatable food, and eating disorders. Eating "comfort foods" in response to a negative emotional state, for example, suggests that some individuals overeat to self-medicate. Clinical data suggest that some individuals may develop addiction-like behaviors from consuming palatable foods. Based on this observation, "food addiction" has emerged as an area of intense scientific research. A growing body of evidence suggests that some aspects of food addiction, such as compulsive eating behavior, can be modeled in animals. Moreover, several areas of the brain, including various neurotransmitter systems, are involved in the reinforcement effects of both food and drugs, suggesting that natural and pharmacological stimuli activate similar neural systems. In addition, several recent studies have identified a putative connection between neural circuits activated in the seeking and intake of both palatable food and drugs. The development of well-characterized animal models will increase our understanding of the etiological factors of food addiction and will help identify the neural substrates involved in eating disorders such as compulsive overeating. Such models will facilitate the development and validation of targeted pharmacological therapies.
Matteo Di Segni
Full Text Available Eating disorders are multifactorial conditions that can involve a combination of genetic, metabolic, environmental, and behavioral factors. Studies in humans and laboratory animals show that eating can also be regulated by factors unrelated to metabolic control. Several studies suggest a link between stress, access to highly palatable food, and eating disorders. Eating “comfort foods” in response to a negative emotional state, for example, suggests that some individuals overeat to self-medicate. Clinical data suggest that some individuals may develop addiction-like behaviors from consuming palatable foods. Based on this observation, “food addiction” has emerged as an area of intense scientific research. A growing body of evidence suggests that some aspects of food addiction, such as compulsive eating behavior, can be modeled in animals. Moreover, several areas of the brain, including various neurotransmitter systems, are involved in the reinforcement effects of both food and drugs, suggesting that natural and pharmacological stimuli activate similar neural systems. In addition, several recent studies have identified a putative connection between neural circuits activated in the seeking and intake of both palatable food and drugs. The development of well-characterized animal models will increase our understanding of the etiological factors of food addiction and will help identify the neural substrates involved in eating disorders such as compulsive overeating. Such models will facilitate the development and validation of targeted pharmacological therapies.
Madsen, Charlotte Bernhard; Kroghsbo, Stine; Bøgh, Katrine Lindholm
evaluation. One of the pitfalls may be the premise that an animal model needs to mimic the disease. Chemical contact sensitizers may be predicted in an animal test, the Local Lymph Node Assay (LLNA). This assay is based on detailed mechanistic knowledge of contact sensitization including knowledge on dose......’t know under what circumstances oral tolerance develops. With all these unanswered questions, it is a big challenge to design an animal model that, with relatively few animals, is able to predict if a food allergen is not only a potential allergen but also predict its potency, a prerequisite for risk...
Amanda R. Panfil
Full Text Available Since the isolation and discovery of human T-cell leukemia virus type 1 (HTLV-1 over 30 years ago, researchers have utilized animal models to study HTLV-1 transmission, viral persistence, virus-elicited immune responses, and HTLV-1-associated disease development (ATL, HAM/TSP. Non-human primates, rabbits, rats, and mice have all been used to help understand HTLV-1 biology and disease progression. Non-human primates offer a model system that is phylogenetically similar to humans for examining viral persistence. Viral transmission, persistence, and immune responses have been widely studied using New Zealand White rabbits. The advent of molecular clones of HTLV-1 has offered the opportunity to assess the importance of various viral genes in rabbits, non-human primates, and mice. Additionally, over-expression of viral genes using transgenic mice has helped uncover the importance of Tax and Hbz in the induction of lymphoma and other lymphocyte-mediated diseases. HTLV-1 inoculation of certain strains of rats results in histopathological features and clinical symptoms similar to that of humans with HAM/TSP. Transplantation of certain types of ATL cell lines in immunocompromised mice results in lymphoma. Recently, “humanized” mice have been used to model ATL development for the first time. Not all HTLV-1 animal models develop disease and those that do vary in consistency depending on the type of monkey, strain of rat, or even type of ATL cell line used. However, the progress made using animal models cannot be understated as it has led to insights into the mechanisms regulating viral replication, viral persistence, disease development, and, most importantly, model systems to test disease treatments.
Kohart, Nicole A; Elshafae, Said M; Breitbach, Justin T; Rosol, Thomas J
Cancer-associated hypercalcemia (CAH) is a frequently-occurring paraneoplastic syndrome that contributes to substantial patient morbidity and occurs in both humans and animals. Patients with CAH are often characterized by markedly elevated serum calcium concentrations that result in a range of clinical symptoms involving the nervous, gastrointestinal and urinary systems. CAH is caused by two principle mechanisms; humorally-mediated and/or through local osteolytic bone metastasis resulting in excessive calcium release from resorbed bone. Humoral hypercalcemia of malignancy (HHM) is the most common mechanism and is due to the production and release of tumor-associated cytokines and humoral factors, such as parathyroid hormone-related protein (PTHrP), that act at distant sites to increase serum calcium concentrations. Local osteolytic hypercalcemia (LOH) occurs when primary or metastatic bone tumors act locally by releasing factors that stimulate osteoclast activity and bone resorption. LOH is a less frequent cause of CAH and in some cases can induce hypercalcemia in concert with HHM. Rarely, ectopic production of parathyroid hormone has been described. PTHrP-mediated hypercalcemia is the most common mechanism of CAH in human and canine malignancies and is recognized in other domestic species. Spontaneous and experimentally-induced animal models have been developed to study the mechanisms of CAH. These models have been essential for the evaluation of novel approaches and adjuvant therapies to manage CAH. This review will highlight the comparative aspects of CAH in humans and animals with a discussion of the available animal models used to study the pathogenesis of this important clinical syndrome.
Workman, Joanna L; Nelson, Randy J
Seasonal affective disorder (SAD) is characterized by depressive episodes during winter that are alleviated during summer and by morning bright light treatment. Currently, there is no animal model of SAD. However, it may be possible to use rodents that respond to day length (photoperiod) to understand how photoperiod can shape the brain and behavior in humans. As nights lengthen in the autumn, the duration of the nightly elevation of melatonin increase; seasonally breeding animals use this information to orchestrate seasonal changes in physiology and behavior. SAD may originate from the extended duration of nightly melatonin secretion during fall and winter. These similarities between humans and rodents in melatonin secretion allows for comparisons with rodents that express more depressive-like responses when exposed to short day lengths. For instance, Siberian hamsters, fat sand rats, Nile grass rats, and Wistar rats display a depressive-like phenotype when exposed to short days. Current research in depression and animal models of depression suggests that hippocampal plasticity may underlie the symptoms of depression and depressive-like behaviors, respectively. It is also possible that day length induces structural changes in human brains. Many seasonally breeding rodents undergo changes in whole brain and hippocampal volume in short days. Based on strict validity criteria, there is no animal model of SAD, but rodents that respond to reduced day lengths may be useful to approximate the neurobiological phenomena that occur in people with SAD, leading to greater understanding of the etiology of the disorder as well as novel therapeutic interventions. Copyright © 2010 Elsevier Ltd. All rights reserved.
van Andel, Mary; Jewell, Christopher; McKenzie, Joanna; Hollings, Tracey; Robinson, Andrew; Burgman, Mark; Bingham, Paul; Carpenter, Tim
Accurate information on the geographic distribution of domestic animal populations helps biosecurity authorities to efficiently prepare for and rapidly eradicate exotic diseases, such as Foot and Mouth Disease (FMD). Developing and maintaining sufficiently high-quality data resources is expensive and time consuming. Statistical modelling of population density and distribution has only begun to be applied to farm animal populations, although it is commonly used in wildlife ecology. We developed zero-inflated Poisson regression models in a Bayesian framework using environmental and socioeconomic variables to predict the counts of livestock units (LSUs) and of cattle on spatially referenced farm polygons in a commercially available New Zealand farm database, Agribase. Farm-level counts of cattle and of LSUs varied considerably by region, because of the heterogeneous farming landscape in New Zealand. The amount of high quality pasture per farm was significantly associated with the presence of both cattle and LSUs. Internal model validation (predictive performance) showed that the models were able to predict the count of the animal population on groups of farms that were located in randomly selected 3km zones with a high level of accuracy. Predicting cattle or LSU counts on individual farms was less accurate. Predicted counts were statistically significantly more variable for farms that were contract grazing dry stock, such as replacement dairy heifers and dairy cattle not currently producing milk, compared with other farm types. This analysis presents a way to predict numbers of LSUs and cattle for farms using environmental and socio-economic data. The technique has the potential to be extrapolated to predicting other pastoral based livestock species. Copyright © 2017 Elsevier B.V. All rights reserved.
Torabinejad, Mahmoud; Corr, Robert; Buhrley, Matthew; Wright, Kenneth; Shabahang, Shahrokh
A growing body of evidence is demonstrating the possibility for regeneration of tissues within the pulp space and continued root development in teeth with necrotic pulps and open apices. There are areas of research related to regenerative endodontics that need to be investigated in an animal model. The purpose of this study was to investigate ferret cuspid teeth as a model to investigate factors involved in regenerative endodontics. Six young male ferrets between the ages of 36-133 days were used in this investigation. Each animal was anesthetized and perfused with 10% buffered formalin. Block sections including the mandibular and maxillary cuspid teeth and their surrounding periapical tissues were obtained, radiographed, decalcified, sectioned, and stained with hematoxylin-eosin to determine various stages of apical closure in these teeth. The permanent mandibular and maxillary cuspid teeth with open apices erupted approximately 50 days after birth. Initial signs of closure of the apical foramen in these teeth were observed between 90-110 days. Complete apical closure was observed in the cuspid teeth when the animals were 133 days old. Based on the experiment, ferret cuspid teeth can be used to investigate various factors involved in regenerative endodontics that cannot be tested in human subjects. The most appropriate time to conduct the experiments would be when the ferrets are between the ages of 50 and 90 days. Copyright Â© 2011. Published by Elsevier Inc.
Gerds, Thomas Alexander; van de Wiel, MA
In medical statistics, many alternative strategies are available for building a prediction model based on training data. Prediction models are routinely compared by means of their prediction performance in independent validation data. If only one data set is available for training and validation......, then rival strategies can still be compared based on repeated bootstraps of the same data. Often, however, the overall performance of rival strategies is similar and it is thus difficult to decide for one model. Here, we investigate the variability of the prediction models that results when the same...... to distinguish rival prediction models with similar prediction performances. Furthermore, on the subject level a confidence score may provide useful supplementary information for new patients who want to base a medical decision on predicted risk. The ideas are illustrated and discussed using data from cancer...
Hatziioannou, Theodora; Evans, David T.
The AIDS pandemic continues to present us with unique scientific and public health challenges. Although the development of effective antiretroviral therapy has been a major triumph, the emergence of drug resistance requires active management of treatment regimens and the continued development of new antiretroviral drugs. Moreover, despite nearly 30 years of intensive investigation, we still lack the basic scientific knowledge necessary to produce a safe and effective vaccine against HIV-1. Animal models offer obvious advantages in the study of HIV/AIDS, allowing for a more invasive investigation of the disease and for preclinical testing of drugs and vaccines. Advances in humanized mouse models, non-human primate immunogenetics and recombinant challenge viruses have greatly increased the number and sophistication of available mouse and simian models. Understanding the advantages and limitations of each of these models is essential for the design of animal studies to guide the development of vaccines and antiretroviral therapies for the prevention and treatment of HIV-1 infection. PMID:23154262
Samaranayake, Yuthika H.; Samaranayake, Lakshman P.
Oral candidiasis is as much the final outcome of the vulnerability of the host as of the virulence of the invading organism. We review here the extensive literature on animal experiments mainly appertaining to the host predisposing factors that initiate and perpetuate these infections. The monkey, rat, and mouse are the choice models for investigating oral candidiasis, but comparisons between the same or different models appear difficult, because of variables such as the study design, the number of animals used, their diet, the differences in Candida strains, and the duration of the studies. These variables notwithstanding, the following could be concluded. (i) The primate model is ideal for investigating Candida-associated denture stomatitis since both erythematous and pseudomembranous lesions have been produced in monkeys with prosthetic plates; they are, however, expensive and difficult to obtain and maintain. (ii) The rat model (both Sprague-Dawley and Wistar) is well proven for observing chronic oral candidal colonization and infection, due to the ease of breeding and handling and their ready availability. (iii) Mice are similar, but in addition there are well characterized variants simulating immunologic and genetic abnormalities (e.g., athymic, euthymic, murine-acquired immune deficiency syndrome, and severe combined immunodeficient models) and hence are used for short-term studies relating the host immune response and oral candidiasis. Nonetheless, an ideal, relatively inexpensive model representative of the human oral environment in ecological and microbiological terms is yet to be described. Until such a model is developed, researchers should pay attention to standardization of the experimental protocols described here to obtain broadly comparable and meaningful data. PMID:11292645
Borkhardt, A.; Sanchez-Garcia, I.; Cobaleda, C.; Hauer, J.
The term ''leukemia'' encompasses a group of diseases with a variable clinical and pathological presentation. Its cellular origin, its biology and the underlying molecular genetic alterations determine the very variable and individual disease phenotype. The focus of this review is to discuss the most important guidelines to be taken into account when we aim at developing an ''ideal'' animal model to study leukemia. The animal model should mimic all the clinical, histological and molecular genetic characteristics of the human phenotype and should be applicable as a clinically predictive model. It should achieve all the requirements to be used as a standardized model adaptive to basic research as well as to pharmaceutical practice. Furthermore it should fulfill all the criteria to investigate environmental risk factors, the role of genomic mutations and be applicable for therapeutic testing. These constraints limit the usefulness of some existing animal models, which are however very valuable for basic research. Hence in this review we will primarily focus on genetically engineered mouse models (GEMMs) to study the most frequent types of childhood leukemia. GEMMs are robust models with relatively low site specific variability and which can, with the help of the latest gene modulating tools be adapted to individual clinical and research questions. Moreover they offer the possibility to restrict oncogene expression to a defined target population and regulate its expression level as well as its timely activity. Until recently it was only possible in individual cases to develop a murin model, which fulfills the above mentioned requirements. Hence the development of new regulatory elements to control targeted oncogene expression should be priority. Tightly controlled and cell specific oncogene expression can then be combined with a knock-in approach and will depict a robust murine model, which enables almost physiologic oncogene
de los Campos, Gustavo; Hickey, John M.; Pong-Wong, Ricardo; Daetwyler, Hans D.; Calus, Mario P. L.
Genomic-enabled prediction is becoming increasingly important in animal and plant breeding and is also receiving attention in human genetics. Deriving accurate predictions of complex traits requires implementing whole-genome regression (WGR) models where phenotypes are regressed on thousands of markers concurrently. Methods exist that allow implementing these large-p with small-n regressions, and genome-enabled selection (GS) is being implemented in several plant and animal breeding programs. The list of available methods is long, and the relationships between them have not been fully addressed. In this article we provide an overview of available methods for implementing parametric WGR models, discuss selected topics that emerge in applications, and present a general discussion of lessons learned from simulation and empirical data analysis in the last decade. PMID:22745228
Rayburn, Elizabeth R; Gao, Liang; Ding, Jiayi; Ding, Hongxia; Shao, Jun; Li, Haibo
This study reviews FDA-approved drugs that negatively impact spermatozoa in animals, as well as how these findings reflect on observations in human male gametes. The FDA drug warning labels included in the DailyMed database and the peer-reviewed literature in the PubMed database were searched for information to identify single-ingredient, FDA-approved prescription drugs with spermatotoxic effects. A total of 235 unique, single-ingredient, FDA-approved drugs reported to be spermatotoxic in animals were identified in the drug labels. Forty-nine of these had documented negative effects on humans in either the drug label or literature, while 31 had no effect or a positive impact on human sperm. For the other 155 drugs that were spermatotoxic in animals, no human data was available. The current animal models are not very effective for predicting human spermatotoxicity, and there is limited information available about the impact of many drugs on human spermatozoa. New approaches should be designed that more accurately reflect the findings in men, including more studies on human sperm in vitro and studies using other systems (ex vivo tissue culture, xenograft models, in silico studies, etc.). In addition, the present data is often incomplete or reported in a manner that prevents interpretation of their clinical relevance. Changes should be made to the requirements for pre-clinical testing, drug surveillance, and the warning labels of drugs to ensure that the potential risks to human fertility are clearly indicated.
Investigations of preclinical biomarkers for major depressive disorder (MDD) encompass the quantification of proteins, peptides, mRNAs, or small molecules in blood or urine of animal models. Most studies aim at characterising the animal model by including the assessment of analytes or hormones affected in depressive patients. The ultimate objective is to validate the model to better understand the neurobiological basis of MDD. Stress hormones or inflammation-related analytes associated with MDD are frequently measured. In contrast, other investigators evaluate peripheral analytes in preclinical models to translate the results in clinical settings afterwards. Large-scale, hypothesis-free studies are performed in MDD models to identify candidate biomarkers. Other studies wish to propose new targets for drug discovery. Animal models endowed with predictive validity are investigated, and the assessment of peripheral analytes, such as stress hormones or immune molecules, is comprised to increase the confidence in the target. Finally, since the mechanism of action of antidepressants is incompletely understood, studies investigating molecular alterations associated with antidepressant treatment may include peripheral analyte levels. In conclusion, preclinical biomarker studies aid the identification of new candidate analytes to be tested in clinical trials. They also increase our understanding of MDD pathophysiology and help to identify new pharmacological targets.
Pandey, Pramod K; Soupir, Michelle L; Ikenberry, Charles
The transport of animal waste pathogens from crop land to streams can potentially elevate pathogen levels in stream water. Applying animal manure into crop land as fertilizers is a common practice in developing as well as in developed countries. Manure application into the crop land, however, can cause potential human health. To control pathogen levels in ambient water bodies such as streams, improving our understanding of pathogen transport at farm scale as well as at watershed scale is required. To understand the impacts of crop land receiving animal waste as fertilizers on stream's pathogen levels, here we investigate pathogen indicator transport at watershed scale. We exploited watershed scale hydrological model to estimate the transport of pathogens from the crop land to streams. Pathogen indicator levels (i.e., E. coli levels) in the stream water were predicted. With certain assumptions, model results are reasonable. This study can be used as guidelines for developing the models for calculating the impacts of crop land's animal manure on stream water
Muhammad Nazrul Somchit
Full Text Available Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model. Methods: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day. Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN and creatinine activities were measured. Results: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine. Conclusion: Results from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.
Julander, Justin G; Siddharthan, Venkatraman
Zika virus (ZIKV) infection can result in serious consequences, including severe congenital manifestations, persistent infection in the testes, and neurologic sequelae. After a pandemic emergence, the virus has spread to much of North and South America and has been introduced to many countries outside of ZIKV-endemic areas as infected travelers return to their home countries. Rodent models have been important in gaining a better understanding of the wide range of disease etiologies associated with ZIKV infection and for the initial phase of developing countermeasures to prevent or treat viral infections. We discuss herein the advantages and disadvantages of small-animal models that have been developed to replicate various aspects of disease associated with ZIKV infection. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: firstname.lastname@example.org.
Morcillo, M. A.
The biokinetic models for many radionuclides are, to a large extent, based on data obtained in experimental animals. The methods used in the experimental development of a biokinetic model can be classified in two groups (i) those applied during the experimental work, which include the activity determination of a given radionuclide at different times and in different biological media such as blood, serum, organs/tissues, urine, bile and faeces and (ii) those methods used for the analysis and study of the experimental data, based in mathematical tools. Some of these methods are reviewed,with special emphasis in the whole body macro autoradiography. To conclude, the contribution that this type of studies can have in two fields of radiation protection is discussed, namely optimization of dosimetric evaluations and decorporation of radionuclides. (Author)
Ménoret, Séverine; Tesson, Laurent; Remy, Séverine; Usal, Claire; Ouisse, Laure-Hélène; Brusselle, Lucas; Chenouard, Vanessa; Anegon, Ignacio
On May 11th and 12th 2017 was held in Nantes, France, the international meeting "Advances in transgenic animal models and techniques" ( http://www.trm.univ-nantes.fr/ ). This biennial meeting is the fifth one of its kind to be organized by the Transgenic Rats ImmunoPhenomic (TRIP) Nantes facility ( http://www.tgr.nantes.inserm.fr/ ). The meeting was supported by private companies (SONIDEL, Scionics computer innovation, New England Biolabs, MERCK, genOway, Journal Disease Models and Mechanisms) and by public institutions (International Society for Transgenic Technology, University of Nantes, INSERM UMR 1064, SFR François Bonamy, CNRS, Région Pays de la Loire, Biogenouest, TEFOR infrastructure, ITUN, IHU-CESTI and DHU-Oncogeffe and Labex IGO). Around 100 participants, from France but also from different European countries, Japan and USA, attended the meeting.
Marsteller, Nathan; Bøgh, Katrine Lindholm; Goodman, Richard E.
Food safety regulators request prediction of allergenicity for newly expressed proteins in genetically modified (GM) crops and in novel foods. Some have suggested using animal models to assess potential allergenicity. A variety of animal models have been used in research to evaluate sensitisation...
Morsink, Maarten C.; Dukers, Danny F.
Animal models have been widely used for studying the physiology and pharmacology of psychiatric and neurological diseases. The concepts of face, construct, and predictive validity are used as indicators to estimate the extent to which the animal model mimics the disease. Currently, we used these three concepts to design a theoretical assignment to…
Full Text Available The development of animal models of dengue virus (DENV infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the ‘vascular-leak’ syndrome seen in severe dengue in humans. Humanized mouse models can sustain DENV replication and show some signs of disease, but further development is needed to validate the immune response. Classically, immunocompetent mice infected with DENV do not manifest disease or else develop paralysis when inoculated intracranially; however, a new model using high doses of DENV has recently been shown to develop hemorrhagic signs after infection. Overall, each model has its advantages and disadvantages and is differentially suited for studies of dengue pathogenesis and immunopathogenesis and/or pre-clinical testing of antiviral drugs and vaccines.
Wojcikowski, Ken; Gobe, Glenda
Animal studies testing medicinal herbs are often misinterpreted by both translational researchers and clinicians due to a lack of information regarding their predictability, human dose equivalent and potential value. The most common mistake is to design or translate an animal study on a milligram per kilogram basis. This can lead to underestimation of the toxicity and/or overestimation of the amount needed for human therapy. Instead, allometric scaling, which involves body surface area, should be used. While the differences in the pharmacokinetic and pharmacodynamic phases between species will inevitably lead to some degree of error in extrapolation of results regardless of the conversion method used, correct design and interpretation of animal studies can provide information that is not able to be provided by in vitro studies, computer modeling or even traditional use. Copyright © 2013 John Wiley & Sons, Ltd.
Murillo, Óscar; El-Haj, Cristina
Multiresistant Gram-positive infections continue to pose a major clinical challenge and the development of new antibiotics is always desirable. Dalbavancin is a lipoglycopeptide with a prolonged half-life that allows long dosing intervals. In experimental models, its activity has been evaluated in distinct models and microorganisms, which limits the conclusions that can be drawn; however, the largest number of studies have been conducted in Staphylococcus aureus infection. Overall, dalbavancin has shown concentration-dependent efficacy and the parameters best explaining its activity are maximal pharmacodynamic concentration/minimal inhibitory concentration and the area under the curve/minimal inhibitory concentration. In these experimental models, dalbavancin has shown good distribution, a prolonged half-life in all animal species and efficacy that is mostly similar to that of previous glycopeptides but with lower doses and with longer dosing intervals. Of note, the efficacy of dalbavancin is not altered by methicillin resistance or the glycopeptide sensitivity of S. aureus. In the case of difficult-to-treat staphylococcal infections (eg, endocarditis, foreign body infections), an adequate dosing interval and high dosage seem to play an important role in the efficacy of the drug. All in all, experimental models can still provide greater knowledge of this new antibiotic to guide clinical research and determine its role in the treatment of distinct infections produced by Gram-positive microorganisms. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.
We consider a statistical prediction problem under misspecified models. In a sense, Bayesian prediction is an optimal prediction method when an assumed model is true. Bootstrap prediction is obtained by applying Breiman's `bagging' method to a plug-in prediction. Bootstrap prediction can be considered to be an approximation to the Bayesian prediction under the assumption that the model is true. However, in applications, there are frequently deviations from the assumed model. In this paper, bo...
Trøstrup, Hannah; Thomsen, Kim; Calum, Henrik
Chronic wounds are a substantial clinical problem affecting millions of people worldwide. Pathophysiologically, chronic wounds are stuck in the inflammatory state of healing. The role of bacterial biofilms in suppression and perturbation of host response could be an explanation for this observation....... An inhibiting effect of bacterial biofilms on wound healing is gaining significant clinical attention over the last few years. There is still a paucity of suitable animal models to recapitulate human chronic wounds. The etiology of the wound (venous insufficiency, ischemia, diabetes, pressure) has to be taken...... into consideration as underlying pathophysiological mechanisms and comorbidities display tremendous variation in humans. Confounders such as infection, smoking, chronological age, sex, medication, metabolic disturbances, and renal impairment add to the difficulty in gaining systematic and comparable studies...
Marti, I.; Nielsen, Torben Skov; Madsen, Henrik
The objective of the work is to investigatethe performance of HIRLAM in complex terrain when used as input to energy production forecasting models, and to develop a statistical model to adapt HIRLAM prediction to the wind farm. The features of the terrain, specially the topography, influence...... the performance of HIRLAM in particular with respect to wind predictions. To estimate the performance of the model two spatial resolutions (0,5 Deg. and 0.2 Deg.) and different sets of HIRLAM variables were used to predict wind speed and energy production. The predictions of energy production for the wind farms...... are calculated using on-line measurements of power production as well as HIRLAM predictions as input thus taking advantage of the auto-correlation, which is present in the power production for shorter pediction horizons. Statistical models are used to discribe the relationship between observed energy production...
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The narrow host range of infection and lack of suitable tissue culture systems for the propagation of hepatitis B and C viruses are limitations that have prevented a more thorough understanding of persistent infection and the pathogenesis of chronic liver disease.
Despite decades of intensive research and significant progresses in understanding of viral hepatitis, many basic questions and clinical problems still await to be resolved. For example, the HBV cellular receptor and related mechanisms of viral entry have not yet been identified. Little is also known about the function of certain non-structural viral products, such as the hepatitis B e antigen and the X protein, or about the role of excess hepadnavirus subviral particles circulating in the blood stream during infection. Furthermore, the molecular mechanisms involved in the development of hepatocellular carcinoma and the role of the immune system in determining the fate of infection are not fully understood.
The reason for these drawbacks is essentially due to the lack of reliable cell-based in vitro infection systems and, most importantly, convenient animal models.
This lack of knowledge has been partially overcome for hepatitis B virus (HBV, by the discovery and characterization of HBV-like viruses in wild animals while for hepatitis C virus (HCV, related flaviviruses have been used as surrogate systems.
Other laboratories have developed transgenic mice that express virus gene products and/or support virus replication. Some HBV transgenic mouse models
Mohan Kumar Pasupuleti
Full Text Available Laboratory animal models serve as a facilitator to investigate the etiopathogenesis of periodontal disease, are used to know the efficacy of reconstructive and regenerative procedures, and are also helpful in evaluation of newer therapeutic techniques including laser and implant therapies prior to application in the human beings. The aim of this review is to know the different animal models used in various specialties of dental research and to know the ethical guidelines prior to the usage of experimental models with main emphasis on how to refine, replace, and reduce the number of animal models usage in the laboratory. An online search for experimental animal models used in dental research was performed using MEDLINE/PubMed database. Publications from 2009 to May 2013 in the specialty of periodontics were included in writing this review. A total of 652 references were published in PubMed/MEDLINE databases based on the search terms used. Out of 245 studies, 241 were related to the periodontal research published in English from 2009 to 2013. Relevant papers were chosen according to the inclusion and exclusion criteria. After extensive electronic and hand search on animal models, it has been observed that various animal models were used in dental research. Search on animal models used for dental research purpose revealed that various animals such as rats, mice, guinea pigs, rabbit, beagle dogs, goats, and nonhuman primates were extensively used. However, with the new advancement of ex vivo animal models, it has become easy to investigate disease pathogenesis and to test the efficacy of newer therapeutic modalities with the reduced usage of animal models. This review summarized the large amount of literature on animal models used in periodontal research with main emphasis on ethical guidelines and on reducing the animal model usage in future perspective.
Jul 2, 2012 ... Linear MPC. 1. Uses linear model: ˙x = Ax + Bu. 2. Quadratic cost function: F = xT Qx + uT Ru. 3. Linear constraints: Hx + Gu < 0. 4. Quadratic program. Nonlinear MPC. 1. Nonlinear model: ˙x = f(x, u). 2. Cost function can be nonquadratic: F = (x, u). 3. Nonlinear constraints: h(x, u) < 0. 4. Nonlinear program.
Cai, Bin; Wang, Ning
Stroke is a leading cause of serious long-term disability worldwide and the second leading cause of death in many countries. Long-time attempts to salvage dying neurons via various neuroprotective agents have failed in stroke translational research, owing in part to the huge gap between animal stroke models and stroke patients, which also suggests that rodent models have limited predictive value and that alternate large animal models are likely to become important in future translational research. The genetic background, physiological characteristics, behavioral characteristics, and brain structure of large animals, especially nonhuman primates, are analogous to humans, and resemble humans in stroke. Moreover, relatively new regional imaging techniques, measurements of regional cerebral blood flow, and sophisticated physiological monitoring can be more easily performed on the same animal at multiple time points. As a result, we can use large animal stroke models to decrease the gap and promote translation of basic science stroke research. At the same time, we should not neglect the disadvantages of the large animal stroke model such as the significant expense and ethical considerations, which can be overcome by rodent models. Rodents should be selected as stroke models for initial testing and primates or cats are desirable as a second species, which was recommended by the Stroke Therapy Academic Industry Roundtable (STAIR) group in 2009.
Roy, Sumit; Laerum, Frode; Brosstad, Frank; Kvernebo, Knut; Sakariassen, Kjell S.
Purpose: To develop an animal model of acute deep vein thrombosis (DVT). Methods: In part I of the study nine juvenile domestic pigs were used. Each external iliac vein was transluminally occluded with a balloon catheter. Thrombin was infused through a microcatheter in one leg according to one of the following protocols: (1) intraarterial (IA): 1250 U at 25 U/min in the common femoral artery (n= 3); (2) intravenous (IV): 5000 U in the popliteal vein at 500 U/min (n= 3), or at 100 U/min (n= 3). Saline was administered in the opposite leg. After the animals were killed, the mass of thrombus in the iliofemoral veins was measured. The pudendoepiploic (PEV), profunda femoris (PF), and popliteal veins (PV) were examined. Thrombosis in the tributaries of the superficial femoral vein (SFVt) was graded according to a three-point scale (0, +, ++). In part II of the study IV administration was further investigated in nine pigs using the following three regimens with 1000 U at 25 U/min serving as the control: (1) 1000 U at 100 U/min, (2) 250 U at 25 U/min, (3) 250 U at 6.25 U/min. Results: All animals survived. In part I median thrombus mass in the test limbs was 1.40 g as compared with 0.25 g in the controls (p= 0.01). PEV, PFV and PV were thrombosed in all limbs infused with thrombin. IV infusion was more effective in inducing thrombosis in both the parent veins (mass 1.32-1.78 g) and SVFt (++ in 4 of 6 legs), as compared with IA infusion (mass 0.0-1.16 g; SFVt ++ in 1 of 3 legs). In part II thrombus mass in axial veins ranged from 1.23 to 2.86 g, and showed no relationship with the dose of thrombin or the rate of infusion. Tributary thrombosis was less extensive with 250 U at 25 U/min than with the other regimens. Conclusion: Slow distal intravenous thrombin infusion in the hind legs of pigs combined with proximal venous occlusion induces thrombosis in the leg veins that closely resembles clinical DVT in distribution
Full Text Available Abstract Background The requirement that animals be used in research and testing in order to protect humans was formalized in the Nuremberg Code and subsequent national and international laws, codes, and declarations. Discussion We review the history of these requirements and contrast what was known via science about animal models then with what is known now. We further analyze the predictive value of animal models when used as test subjects for human response to drugs and disease. We explore the use of animals for models in toxicity testing as an example of the problem with using animal models. Summary We conclude that the requirements for animal testing found in the Nuremberg Code were based on scientifically outdated principles, compromised by people with a vested interest in animal experimentation, serve no useful function, increase the cost of drug development, and prevent otherwise safe and efficacious drugs and therapies from being implemented.
Greek, Ray; Pippus, Annalea; Hansen, Lawrence A
The requirement that animals be used in research and testing in order to protect humans was formalized in the Nuremberg Code and subsequent national and international laws, codes, and declarations. We review the history of these requirements and contrast what was known via science about animal models then with what is known now. We further analyze the predictive value of animal models when used as test subjects for human response to drugs and disease. We explore the use of animals for models in toxicity testing as an example of the problem with using animal models. We conclude that the requirements for animal testing found in the Nuremberg Code were based on scientifically outdated principles, compromised by people with a vested interest in animal experimentation, serve no useful function, increase the cost of drug development, and prevent otherwise safe and efficacious drugs and therapies from being implemented.
Full Text Available An intensive research from academics and practitioners has been provided regarding models for bankruptcy prediction and credit risk management. In spite of numerous researches focusing on forecasting bankruptcy using traditional statistics techniques (e.g. discriminant analysis and logistic regression and early artificial intelligence models (e.g. artificial neural networks, there is a trend for transition to machine learning models (support vector machines, bagging, boosting, and random forest to predict bankruptcy one year prior to the event. Comparing the performance of this with unconventional approach with results obtained by discriminant analysis, logistic regression, and neural networks application, it has been found that bagging, boosting, and random forest models outperform the others techniques, and that all prediction accuracy in the testing sample improves when the additional variables are included. On the other side the prediction accuracy of old and well known bankruptcy prediction models is quiet high. Therefore, we aim to analyse these in some way old models on the dataset of Slovak companies to validate their prediction ability in specific conditions. Furthermore, these models will be modelled according to new trends by calculating the influence of elimination of selected variables on the overall prediction ability of these models.
Granton A. Jindal
Full Text Available RASopathies are developmental disorders caused by germline mutations in the Ras-MAPK pathway, and are characterized by a broad spectrum of functional and morphological abnormalities. The high incidence of these disorders (∼1/1000 births motivates the development of systematic approaches for their efficient diagnosis and potential treatment. Recent advances in genome sequencing have greatly facilitated the genotyping and discovery of mutations in affected individuals, but establishing the causal relationships between molecules and disease phenotypes is non-trivial and presents both technical and conceptual challenges. Here, we discuss how these challenges could be addressed using genetically modified model organisms that have been instrumental in delineating the Ras-MAPK pathway and its roles during development. Focusing on studies in mice, zebrafish and Drosophila, we provide an up-to-date review of animal models of RASopathies at the molecular and functional level. We also discuss how increasingly sophisticated techniques of genetic engineering can be used to rigorously connect changes in specific components of the Ras-MAPK pathway with observed functional and morphological phenotypes. Establishing these connections is essential for advancing our understanding of RASopathies and for devising rational strategies for their management and treatment.
Developing statistical models that estimate the probability of developing melanoma cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.
Degree-day models link ambient temperature to insect life-stages, making such models valuable tools in integrated pest management. These models increase management efficacy by predicting pest phenology. In Wisconsin, the top insect pest of cranberry production is the cranberry fruitworm, Acrobasis v...
Full Text Available Revealing the mechanisms of neoplastic disease and enhancing our ability to intervene in these processes requires an increased understanding of cellular and molecular changes as they occur in intact living animal models. We have begun to address these needs by developing a method of labeling tumor cells through constitutive expression of an optical reporter gene, noninvasively monitoring cellular proliferation in vivo using a sensitive photon detection system. A stable line of HeLa cells that expressed a modified firefly luciferase gene was generated, proliferation of these cells in irradiated severe combined immunodeficiency (SCID mice was monitored. Tumor cells were introduced into animals via subcutaneous, intraperitoneal and intravenous inoculation and whole body images, that revealed tumor location and growth kinetics, were obtained. The number of photons that were emitted from the labeled tumor cells and transmitted through murine tissues was sufficient to detect 1×103 cells in the peritoneal cavity, 1×104 cells at subcutaneous sites and 1×106 circulating cells immediately following injection. The kinetics of cell proliferation, as measured by photon emission, was exponential in the peritoneal cavity and at subcutaneous sites. Intravenous inoculation resulted in detectable colonies of tumor cells in animals receiving more than 1×103 cells. Our demonstrated ability to detect small numbers of tumor cells in living animals noninvasively suggests that therapies designed to treat minimal disease states, as occur early in the disease course and after elimination of the tumor mass, may be monitored using this approach. Moreover, it may be possible to monitor micrometastases and evaluate the molecular steps in the metastatic process. Spatiotemporal analyses of neoplasia will improve the predictability of animal models of human disease as study groups can be followed over time, this method will accelerate development of novel therapeutic
EPA’s ‘virtual embryo’ project is building an integrative systems biology framework for predictive models of developmental toxicity. One schema involves a knowledge-driven adverse outcome pathway (AOP) framework utilizing information from public databases, standardized ontologies...
Boggiano, M M; Artiga, A I; Pritchett, C E; Chandler-Laney, P C; Smith, M L; Eldridge, A J
To determine the stability of individual differences in non-nutritive 'junk' palatable food (PF) intake in rats; assess the relationship of these differences to binge-eating characteristics and susceptibility to obesity; and evaluate the practicality of using these differences to model binge-eating and obesity. Binge-eating prone (BEP) and resistant (BER) groups were identified. Differential responses to stress, hunger, macronutrient-varied PFs, a diet-induced obesity (DIO) regimen and daily vs intermittent access to a PF+chow diet, were assessed. One hundred and twenty female Sprague-Dawley rats. Reliability of intake patterns within rats; food intake and body weight after various challenges over acute (1, 2, 4 h), 24-h and 2-week periods. Although BEP and BER rats did not differ in amount of chow consumed, BEPs consumed >50% more intermittent PF than BERs (PBEPs suppressed chow but not PF intake when stressed, and ate as much when sated as when hungry. Conversely, BERs were more affected by stress and ate less PF, not chow, when stressed and were normally hyperphagic to energy deficit. BEP overeating generalized to other PFs varying in sucrose, fat and nutrition content. Half the rats in each group proved to be obesity prone after a no-choice high fat diet (DIO diet) but a continuous diet of PF+chow normalized the BEPs high drive for PF. Greater intermittent intake of PF predicts binge-eating independent of susceptibility to weight gain. Daily fat consumption in a nutritious source (DIO-diet; analogous to a fatty meal) promoted overeating and weight gain but limiting fat to daily non-nutritive food (PF+chow; analogous to a snack with a low fat meal), did not. The data offer an animal model of lean and obese binge-eating, and obesity with and without binge-eating that can be used to identify the unique physiology of these groups and henceforth suggest more specifically targeted treatments for binge-eating and obesity.
Greek, Ray; Pippus, Annalea; Hansen, Lawrence A
Abstract Background The requirement that animals be used in research and testing in order to protect humans was formalized in the Nuremberg Code and subsequent national and international laws, codes, and declarations. Discussion We review the history of these requirements and contrast what was known via science about animal models then with what is known now. We further analyze the predictive...
Full Text Available Abstract Background Genetic evaluation models often include genetic groups to account for unequal genetic level of animals with unknown parentage. The definition of phantom parent groups usually includes a time component (e.g. years. Combining several time periods to ensure sufficiently large groups may create problems since all phantom parents in a group are considered contemporaries. Methods To avoid the downside of such distinct classification, a fuzzy logic approach is suggested. A phantom parent can be assigned to several genetic groups, with proportions between zero and one that sum to one. Rules were presented for assigning coefficients to the inverse of the relationship matrix for fuzzy-classified genetic groups. This approach was illustrated with simulated data from ten generations of mass selection. Observations and pedigree records were randomly deleted. Phantom parent groups were defined on the basis of gender and generation number. In one scenario, uncertainty about generation of birth was simulated for some animals with unknown parents. In the distinct classification, one of the two possible generations of birth was randomly chosen to assign phantom parents to genetic groups for animals with simulated uncertainty, whereas the phantom parents were assigned to both possible genetic groups in the fuzzy classification. Results The empirical prediction error variance (PEV was somewhat lower for fuzzy-classified genetic groups. The ranking of animals with unknown parents was more correct and less variable across replicates in comparison with distinct genetic groups. In another scenario, each phantom parent was assigned to three groups, one pertaining to its gender, and two pertaining to the first and last generation, with proportion depending on the (true generation of birth. Due to the lower number of groups, the empirical PEV of breeding values was smaller when genetic groups were fuzzy-classified. Conclusion Fuzzy
Full Text Available The contribution is oriented to basic problem trends solution of economic pointers, using neural networks. Problems include choice of the suitable model and consequently configuration of neural nets, choice computational function of neurons and the way prediction learning. The contribution contains two basic models that use structure of multilayer neural nets and way of determination their configuration. It is postulate a simple rule for teaching period of neural net, to get most credible prediction.Experiments are executed with really data evolution of exchange rate Kč/Euro. The main reason of choice this time series is their availability for sufficient long period. In carry out of experiments the both given basic kind of prediction models with most frequent use functions of neurons are verified. Achieve prediction results are presented as in numerical and so in graphical forms.
Full Text Available Wound healing and reduction of its recovery time is one of the most important issues in medicine. Wound is defined as disruption of anatomy and function of normal skin. This injury could be the result of physical elements such as surgical incision, hit or pressure cut of the skin and gunshot wound. Chemical or caustic burn is another category of wound causes that can be induced by acid or base contact irritation. Healing is a process of cellular and extracellular matrix interactions that occur in the damaged tissue. Wound healing consists of several stages including hemostasis, inflammatory phase, proliferative phase and new tissue formation which reconstructs by new collagen formation. Wounds are divided into acute and chronic types based on their healing time. Acute wounds have sudden onset and in normal individuals usually have healing process of less than 4 weeks without any residual side effects. In contrast, chronic wounds have gradual onset. Their inflammatory phase is prolonged and the healing process is stopped due to some background factors like diabetes, ischemia or local pressure. If the healing process lasts more than 4 weeks it will be classified as chronic wound. Despite major advances in the treatment of wounds, still finding effective modalities for healing wounds in the shortest possible time with the fewest side effects is a current challenge. In this review different phases of wound healing and clinical types of wound such as venous leg ulcer, diabetic foot ulcer and pressure ulcer are discussed. Also acute wound models (i.e burn wounds or incisional wound and chronic wound models (such as venous leg ulcers, diabetic foot ulcer, pressure ulcers or bedsore in laboratory animals are presented. This summary can be considered as a preliminary step to facilitate designing of more targeted and applied research in this area.
Can the material properties of regenerate bone be predicted with non-invasive methods of assessment? Exploring the correlation between dual X-ray absorptiometry and compression testing to failure in an animal model of distraction osteogenesis.
Monsell, Fergal; Hughes, Andrew William; Turner, James; Bellemore, Michael C; Bilston, Lynne
Evaluation of the material properties of regenerate bone is of fundamental importance to a successful outcome following distraction osteogenesis using an external fixator. Plain radiographs are in widespread use for assessment of alignment and the distraction gap but are unable to detect bone formation in the early stages of distraction osteogenesis and do not quantify accurately the structural properties of the regenerate. Dual X-ray absorptiometry (DXA) is a widely available non-invasive imaging modality that, unlike X-ray, can be used to measure bone mineral content (BMC) and density quantitatively. In order to be useful as a clinical investigation; however, the structural two-dimensional geometry and density distributions assessed by DXA should reflect material properties such as modulus and also predict the structural mechanical properties of the regenerate bone formed. We explored the hypothesis that there is a relationship between DXA assessment of regenerate bone and structural mechanical properties in an animal model of distraction osteogenesis. Distraction osteogenesis was carried out on the tibial diaphysis of 41 male, 12 week old, New Zealand white rabbits as part of a larger study. Distraction started after a latent period of 24 h at a rate of 0.375 mm every 12 h and continued for 10-days, achieving average lengthening of 7.1 mm. Following an 18-day period of consolidation, the regenerate bone was subject to bone density measurements using a total body dual-energy X-ray densitometer. This produced measurement of BMC, bone mineral density (BMD) and volumetric bone mineral density (vBMD). The tibiae were then disarticulated and cleaned of soft tissue before loading in compression to failure using an Instron mechanical testing machine (Instron Corporation, Massachusetts USA). Using Spearman rank correlation and linear regression, there was a significant correlation between vBMD and the Modulus of Elasticity, Yield Stress and Failure Stress of the
Ambalavanan, Namasivayam; Morty, Rory E
There have been many efforts to develop good animal models of bronchopulmonary dysplasia (BPD) to better understand the pathophysiology and mechanisms underlying development of BPD as well as to test potential strategies for its prevention and treatment. This Perspectives summarizes the features of common animal models of BPD and the strengths and limitations of such models. Potential optimal approaches to development of animal models are indicated, with the underlying concepts that require emphasis. Copyright © 2016 the American Physiological Society.
Lebreton, Jean-Dominique; Nichols, James D.; Barker, Richard J.; Pradel, Roger; Spendelow, Jeffrey A.
Many fields of science begin with a phase of exploration and description, followed by investigations of the processes that account for observed patterns. The science of ecology is no exception, and recent decades have seen a focus on understanding key processes underlying the dynamics of ecological systems. In population ecology, emphasis has shifted from the state variable of population size to the demographic processes responsible for changes in this state variable: birth, death, immigration, and emigration. In evolutionary ecology, some of these same demographic processes, rates of birth and death, are also the determinants of fitness. In animal population ecology, the estimation of state variables and their associated vital rates is especially problematic because of the difficulties in sampling such populations and detecting individual animals. Indeed, early capture–recapture models were developed for the purpose of estimating population size, given the reality that all animals are not caught or detected at any sampling occasion. More recently, capture–recapture models for open populations were developed to draw inferences about survival in the face of these same sampling problems. The focus of this paper is on multi‐state mark–recapture models (MSMR), which first appeared in the 1970s but have undergone substantial development in the last 15 years. These models were developed to deal explicitly with biological variation, in that animals in different “states” (classes defined by location, physiology, behavior, reproductive status, etc.) may have different probabilities of survival and detection. Animal transitions between states are also stochastic and themselves of interest. These general models have proven to be extremely useful and provide a way of thinking about a remarkably wide range of important ecological processes. These methods are now at a stage of refinement and sophistication where they can readily be used by biologists to tackle a wide
This exegesis focuses on the investigative and studio research informing the digital construction of a diverse selection of Australian animals. A series of case studies of digital creature construction - the Jackie Dragon, Jabiru, Bandicoot, Eel, Blue Ringed Octopus and Fiddler Crab - will be outlined along with the key creation study of the Groper. Through investigating how visual research can inform the creation of 3D modelled and animated animal subjects and tracing their development proce...
Sun, C; Madsen, P; Nielsen, U S
Comparisons between a sire model, a sire-dam model, and an animal model were carried out to evaluate the ability of the models to predict breeding values of fertility traits, based on data including 471,742 records from the first lactation of Danish Holstein cows, covering insemination years from...
Blain, John M
Smoothly Leads Users into the Subject of Computer Graphics through the Blender GUIBlender, the free and open source 3D computer modeling and animation program, allows users to create and animate models and figures in scenes, compile feature movies, and interact with the models and create video games. Reflecting the latest version of Blender, The Complete Guide to Blender Graphics: Computer Modeling & Animation, 2nd Edition helps beginners learn the basics of computer animation using this versatile graphics program. This edition incorporates many new features of Blender, including developments
Koehler, Kathryn; Guo, Fei; Zhang, Sheng; Eckstein, Miguel P.
Saliency models have been frequently used to predict eye movements made during image viewing without a specified task (free viewing). Use of a single image set to systematically compare free viewing to other tasks has never been performed. We investigated the effect of task differences on the ability of three models of saliency to predict the performance of humans viewing a novel database of 800 natural images. We introduced a novel task where 100 observers made explicit perceptual judgments about the most salient image region. Other groups of observers performed a free viewing task, saliency search task, or cued object search task. Behavior on the popular free viewing task was not best predicted by standard saliency models. Instead, the models most accurately predicted the explicit saliency selections and eye movements made while performing saliency judgments. Observers' fixations varied similarly across images for the saliency and free viewing tasks, suggesting that these two tasks are related. The variability of observers' eye movements was modulated by the task (lowest for the object search task and greatest for the free viewing and saliency search tasks) as well as the clutter content of the images. Eye movement variability in saliency search and free viewing might be also limited by inherent variation of what observers consider salient. Our results contribute to understanding the tasks and behavioral measures for which saliency models are best suited as predictors of human behavior, the relationship across various perceptual tasks, and the factors contributing to observer variability in fixational eye movements. PMID:24618107
Johansson, Henrik; Lindstedt, Malin
Regulatory frameworks within the European Union demand that chemical substances are investigated for their ability to induce sensitization, an adverse health effect caused by the human immune system in response to chemical exposure. A recent ban on the use of animal tests within the cosmetics industry has led to an urgent need for alternative animal-free test methods that can be used for assessment of chemical sensitizers. To date, no such alternative assay has yet completed formal validation. However, a number of assays are in development and the understanding of the biological mechanisms of chemical sensitization has greatly increased during the last decade. In this MiniReview, we aim to summarize and give our view on the recent progress of method development for alternative assessment of chemical sensitizers. We propose that integrated testing strategies should comprise complementary assays, providing measurements of a wide range of mechanistic events, to perform well-educated risk assessments based on weight of evidence. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
Full Text Available The paper deals with the new algorithm of animation of 3D model of the human head in combination with its global motion. The designed algorithm is very fast and with low calculation requirements, because it does not need the synthesis of the input videosequence for estimation of the animation parameters as well as the parameters of global motion. The used 3D model Candide generates different expressions using its animation units which are controlled by the animation parameters. These ones are estimated on the basis of optical flow without the need of extracting of the feature points in the frames of the input videosequence because they are given by the selected vertices of the animation units of the calibrated 3D model Candide. The established multiple iterations inside the designed animation algorithm of 3D model of the human head between two successive frames significantly improved its accuracy above all for the large motion.
Nataliya O. Bugayets
Full Text Available The article deals with the methodical features in training of computer simulation of systems and processes using animation. In the article the importance of visibility of educational material that combines sensory and thinking sides of cognition is noted. The concept of modeling and the process of building models has been revealed. Attention is paid to the development of skills that are essential for effective learning of animated simulation by visual aids. The graphical environment tools of the computer mathematics system Maxima for animated simulation are described. The examples of creation of models animated visual aids and their use for the development of research skills are presented.
Matteo Di Segni; Enrico Patrono; Loris Patella; Stefano Puglisi-Allegra; Rossella Ventura
Eating disorders are multifactorial conditions that can involve a combination of genetic, metabolic, environmental, and behavioral factors. Studies in humans and laboratory animals show that eating can also be regulated by factors unrelated to metabolic control. Several studies suggest a link between stress, access to highly palatable food, and eating disorders. Eating “comfort foods” in response to a negative emotional state, for example, suggests that some individuals overeat to self-medica...
Bovenkerk, B.; Kaldewaij, F.
Animal models are used in experiments in the behavioural neurosciences that aim to contribute to the prevention and treatment of cognitive and affective disorders in human beings, such as anxiety and depression. Ironically, those animals that are likely to be the best models for psychopathology are
Bovenkerk, Bernice; Kaldewaij, Frederike
Animal models are used in experiments in the behavioural neurosciences that aim to contribute to the prevention and treatment of cognitive and affective disorders in human beings, such as anxiety and depression. Ironically, those animals that are likely to be the best models for psychopathology are
Koolhaas, Jaap M.; Boer, Sietse F. de; Buwalda, Bauke
Animal models have contributed considerably to the current understanding of mechanisms underlying the role of stress in health and disease. Despite the progress made already, much more can be made by more carefully exploiting animals' and humans' shared biology, using ecologically relevant models.
Full Text Available We will review the main animal models for the major neuropsychiatric disorders, focusing on schizophrenia, Alzheimer’s disease, Parkinson’s disease, depression, anxiety and autism. Although these mental disorders are specifically human pathologies and therefore impossible to perfectly replicate in animals, the use of experimental animals is based on the physiological and anatomical similarities between humans and animals such as the rat, and mouse, and on the fact that 99% of human and murine genomes are shared. Pathological conditions in animals can be assessed by manipulating the metabolism of neurotransmitters, through various behavioral tests, and by determining biochemical parameters that can serve as important markers of disorders.
Ahmadou H Dicko
Full Text Available African animal trypanosomosis (AAT is a major constraint to sustainable development of cattle farming in sub-Saharan Africa. The habitat of the tsetse fly vector is increasingly fragmented owing to demographic pressure and shifts in climate, which leads to heterogeneous risk of cyclical transmission both in space and time. In Burkina Faso and Ghana, the most important vectors are riverine species, namely Glossina palpalis gambiensis and G. tachinoides, which are more resilient to human-induced changes than the savannah and forest species. Although many authors studied the distribution of AAT risk both in space and time, spatio-temporal models allowing predictions of it are lacking.We used datasets generated by various projects, including two baseline surveys conducted in Burkina Faso and Ghana within PATTEC (Pan African Tsetse and Trypanosomosis Eradication Campaign national initiatives. We computed the entomological inoculation rate (EIR or tsetse challenge using a range of environmental data. The tsetse apparent density and their infection rate were separately estimated and subsequently combined to derive the EIR using a "one layer-one model" approach. The estimated EIR was then projected into suitable habitat. This risk index was finally validated against data on bovine trypanosomosis. It allowed a good prediction of the parasitological status (r2 = 67%, showed a positive correlation but less predictive power with serological status (r2 = 22% aggregated at the village level but was not related to the illness status (r2 = 2%.The presented spatio-temporal model provides a fine-scale picture of the dynamics of AAT risk in sub-humid areas of West Africa. The estimated EIR was high in the proximity of rivers during the dry season and more widespread during the rainy season. The present analysis is a first step in a broader framework for an efficient risk management of climate-sensitive vector-borne diseases.
Smith, J David; Zakrzewski, Alexandria C; Church, Barbara A
Ongoing research explores whether animals have precursors to metacognition-that is, the capacity to monitor mental states or cognitive processes. Comparative psychologists have tested apes, monkeys, rats, pigeons, and a dolphin using perceptual, memory, foraging, and information-seeking paradigms. The consensus is that some species have a functional analog to human metacognition. Recently, though, associative modelers have used formal-mathematical models hoping to describe animals' "metacognitive" performances in associative-behaviorist ways. We evaluate these attempts to reify formal models as proof of particular explanations of animal cognition. These attempts misunderstand the content and proper application of models. They embody mistakes of scientific reasoning. They blur fundamental distinctions in understanding animal cognition. They impede theoretical development. In contrast, an energetic empirical enterprise is achieving strong success in describing the psychology underlying animals' metacognitive performances. We argue that this careful empirical work is the clear path to useful theoretical development. The issues raised here about formal modeling-in the domain of animal metacognition-potentially extend to biobehavioral research more broadly.
van Meer, Peter J K; Graham, Melanie L; Schuurman, Henk-Jan
Nonclinical studies in animals are conducted to demonstrate proof-of-concept, mechanism of action and safety of new drugs. For a large part, in particular safety assessment, studies are done in compliance with international regulatory guidance. However, animal models supporting the initiation of clinical trials have their limitations, related to uncertainty regarding the predictive value for a clinical condition. The 3Rs principles (refinement, reduction and replacement) are better applied nowadays, with a more comprehensive application with respect to the original definition. This regards also regulatory guidance, so that opportunities exist to revise or reduce regulatory guidance with the perspective that the optimal balance between scientifically relevant data and animal wellbeing or a reduction in animal use can be achieved. In this manuscript we review the connections in the triangle between nonclinical efficacy/safety studies and regulatory aspects, with focus on in vivo testing of drugs. These connections differ for different drugs (chemistry-based low molecular weight compounds, recombinant proteins, cell therapy or gene therapy products). Regarding animal models and their translational value we focus on regulatory aspects and indications where scientific outcomes warrant changes, reduction or replacement, like for, e.g., biosimilar evaluation and safety testing of monoclonal antibodies. On the other hand, we present applications where translational value has been clearly demonstrated, e.g., immunosuppressives in transplantation. Especially for drugs of more recent date like recombinant proteins, cell therapy products and gene therapy products, a regulatory approach that allows the possibility to conduct combined efficacy/safety testing in validated animal models should strengthen scientific outcomes and improve translational value, while reducing the numbers of animals necessary. Copyright © 2015 Elsevier B.V. All rights reserved.
Mutagenicity and carcinogenicity are endpoints of major environmental and regulatory concern. These endpoints are also important targets for development of alternative methods for screening and prediction due to the large number of chemicals of potential concern and the tremendous cost (in time, money, animals) of rodent carcinogenicity bioassays. Both mutagenicity and carcinogenicity involve complex, cellular processes that are only partially understood. Advances in technologies and generation of new data will permit a much deeper understanding. In silico methods for predicting mutagenicity and rodent carcinogenicity based on chemical structural features, along with current mutagenicity and carcinogenicity data sets, have performed well for local prediction (i.e., within specific chemical classes), but are less successful for global prediction (i.e., for a broad range of chemicals). The predictivity of in silico methods can be improved by improving the quality of the data base and endpoints used for modelling. In particular, in vitro assays for clastogenicity need to be improved to reduce false positives (relative to rodent carcinogenicity) and to detect compounds that do not interact directly with DNA or have epigenetic activities. New assays emerging to complement or replace some of the standard assays include VitotoxTM, GreenScreenGC, and RadarScreen. The needs of industry and regulators to assess thousands of compounds necessitate the development of high-t
Tsibulsky, Vladimir L; Norman, Andrew B
This review is focused on mathematical modeling of behaviors of a whole organism with special emphasis on models with a clearly scientific approach to the problem that helps to understand the mechanisms underlying behavior. The aim is to provide an overview of old and contemporary mathematical models without complex mathematical details. Only deterministic and stochastic, but not statistical models are reviewed. All mathematical models of behavior can be divided into two main classes. First, models that are based on the principle of teleological determinism assume that subjects choose the behavior that will lead them to a better payoff in the future. Examples are game theories and operant behavior models both of which are based on the matching law. The second class of models are based on the principle of causal determinism, which assume that subjects do not choose from a set of possibilities but rather are compelled to perform a predetermined behavior in response to specific stimuli. Examples are perception and discrimination models, drug effects models and individual-based population models. A brief overview of the utility of each mathematical model is provided for each section.
Lozier, Jay N.; Nichols, Timothy C.
Animal models of hemophilia and related diseases are important for development of novel treatments and to understand the pathophysiology of bleeding disorders in humans. Testing in animals with the equivalent human disorder provides informed estimates of doses and measures of efficacy, which aids in design of human trials. Many models of hemophilia A, hemophilia B, and von Willebrand disease have been developed from animals with spontaneous mutations (hemophilia A dogs, rats, sheep; hemophilia B dogs; and von Willebrand disease pigs and dogs), or by targeted gene disruption in mice to create hemophilia A, B, or VWD models. Animal models have been used to generate new insights into the pathophysiology of each bleeding disorder and also to perform pre-clinical assessments of standard protein replacement therapies as well as novel gene transfer technology. Both the differences between species and differences in underlying causative mutations must be considered in choosing the best animal for a specific scientific study PMID:23956467
Althea A ArchMiller
Full Text Available Logistic regression models-or "sightability models"-fit to detection/non-detection data from marked individuals are often used to adjust for visibility bias in later detection-only surveys, with population abundance estimated using a modified Horvitz-Thompson (mHT estimator. More recently, a model-based alternative for analyzing combined detection/non-detection and detection-only data was developed. This approach seemed promising, since it resulted in similar estimates as the mHT when applied to data from moose (Alces alces surveys in Minnesota. More importantly, it provided a framework for developing flexible models for analyzing multiyear detection-only survey data in combination with detection/non-detection data. During initial attempts to extend the model-based approach to multiple years of detection-only data, we found that estimates of detection probabilities and population abundance were sensitive to the amount of detection-only data included in the combined (detection/non-detection and detection-only analysis. Subsequently, we developed a robust hierarchical modeling approach where sightability model parameters are informed only by the detection/non-detection data, and we used this approach to fit a fixed-effects model (FE model with year-specific parameters and a temporally-smoothed model (TS model that shares information across years via random effects and a temporal spline. The abundance estimates from the TS model were more precise, with decreased interannual variability relative to the FE model and mHT abundance estimates, illustrating the potential benefits from model-based approaches that allow information to be shared across years.
ArchMiller, Althea A.; Dorazio, Robert; St. Clair, Katherine; Fieberg, John R.
Logistic regression models—or “sightability models”—fit to detection/non-detection data from marked individuals are often used to adjust for visibility bias in later detection-only surveys, with population abundance estimated using a modified Horvitz-Thompson (mHT) estimator. More recently, a model-based alternative for analyzing combined detection/non-detection and detection-only data was developed. This approach seemed promising, since it resulted in similar estimates as the mHT when applied to data from moose (Alces alces) surveys in Minnesota. More importantly, it provided a framework for developing flexible models for analyzing multiyear detection-only survey data in combination with detection/non-detection data. During initial attempts to extend the model-based approach to multiple years of detection-only data, we found that estimates of detection probabilities and population abundance were sensitive to the amount of detection-only data included in the combined (detection/non-detection and detection-only) analysis. Subsequently, we developed a robust hierarchical modeling approach where sightability model parameters are informed only by the detection/non-detection data, and we used this approach to fit a fixed-effects model (FE model) with year-specific parameters and a temporally-smoothed model (TS model) that shares information across years via random effects and a temporal spline. The abundance estimates from the TS model were more precise, with decreased interannual variability relative to the FE model and mHT abundance estimates, illustrating the potential benefits from model-based approaches that allow information to be shared across years.
Na, Woonsung; Yeom, Minjoo; Choi, Il-Kyu; Yook, Heejun; Song, Daesub
Dengue fever is a tropical endemic disease; however, because of climate change, it may become a problem in South Korea in the near future. Research on vaccines for dengue fever and outbreak preparedness are currently insufficient. In addition, because there are no appropriate animal models, controversial results from vaccine efficacy assessments and clinical trials have been reported. Therefore, to study the mechanism of dengue fever and test the immunogenicity of vaccines, an appropriate animal model is urgently needed. In addition to mouse models, more suitable models using animals that can be humanized will need to be constructed. In this report, we look at the current status of model animal construction and discuss which models require further development.
Williams, J. R.; Zhang, Y.; Zhou, H.; Osman, M.; Cha, D.; Kavet, R.; Cuccinotta, F.; Dicello, J. F.; Dillehay, L. E.
The radiation space environment includes particles such as protons and multiple species of heavy ions, with much of the exposure to these radiations occurring at extremely low average dose-rates. Limitations in databases needed to predict cancer hazards in human beings from such radiations are significant and currently do not provide confidence that such predictions are acceptably precise or accurate. In this article, we outline the need for animal carcinogenesis data based on a more sophisticated understanding of the dose-response relationship for induction of cancer and correlative cellular endpoints by representative space radiations. We stress the need for a model that can interrelate human and animal carcinogenesis data with cellular mechanisms. Using a broad model for dose-response patterns which we term the "subalpha-alpha-omega (SAO) model", we explore examples in the literature for radiation-induced cancer and for radiation-induced cellular events to illustrate the need for data that define the dose-response patterns more precisely over specific dose ranges, with special attention to low dose, low dose-rate exposure. We present data for multiple endpoints in cells, which vary in their radiosensitivity, that also support the proposed model. We have measured induction of complex chromosome aberrations in multiple cell types by two space radiations, Fe-ions and protons, and compared these to photons delivered at high dose-rate or low dose-rate. Our data demonstrate that at least three factors modulate the relative efficacy of Fe-ions compared to photons: (i) intrinsic radiosensitivity of irradiated cells; (ii) dose-rate; and (iii) another unspecified effect perhaps related to reparability of DNA lesions. These factors can produce respectively up to at least 7-, 6- and 3-fold variability. These data demonstrate the need to understand better the role of intrinsic radiosensitivity and dose-rate effects in mammalian cell response to ionizing radiation. Such
Skuterud, L.; Strand, P.; Howard, B.J.
The radionuclides of most concern with respect to contamination of animals after a nuclear accident are radioiodine, radiocaesium and radiostrontium (ICRP 30, 1979). Of the other significant anthropogenic radionuclides likely to be released in most accidents, only small proportions of that ingested will be absorbed in an animals gut, and the main animal products, milk and meat, will not normally be contaminated to a significant extent. Animal products will mostly be contaminated as a result of ingestion of contaminated feed and possibly, but to a much lesser extent, from inhalation (for radioiodine only). Direct external contamination of animals is of little or no consequence in human food production. Radioiodine and radiostrontium are important with respect to contamination of milk; radiocaesium contaminates both milk and meat. The physical and chemical form of a radionuclide can influence its absorption in the animal gut. For example, following the Chernobyl accident radiocaesium incorporated into vegetation by root uptake was more readily absorbed than that associated with the original deposit. The transfer of radiocaesium and radiostrontium to animals will be presented both as transfer coefficients and aggregated transfer coefficients. For most animal meat products, only radiocaesium is important as other radionuclides do not significantly contaminate muscle. Farm animal products are the most important foodstuff determining radiocaesium intake by the average consumer in the Nordic countries. The major potential source of radioiodine and radiostrontium to humans is milk and milk products. Of the different species, the smaller animals have the highest transfer of radiocaesium from fodder to meat and milk. (EG)
Tania, Mousumi; Khan, Md Asaduzzaman; Xia, Kun
Autism, a lifelong neuro-developmental disorder is a uniquely human condition. Animal models are not the perfect tools for the full understanding of human development and behavior, but they can be an important place to start. This review focused on the recent updates of animal model research in autism. We have reviewed the publications over the last three decades, which are related to animal model study in autism. Animal models are important because they allow researchers to study the underlying neurobiology in a way that is not possible in humans. Improving the availability of better animal models will help the field to increase the development of medicines that can relieve disabling symptoms. Results from the therapeutic approaches are encouraging remarkably, since some behavioral alterations could be reversed even when treatment was performed on adult mice. Finding an animal model system with similar behavioral tendencies as humans is thus vital for understanding the brain mechanisms, supporting social motivation and attention, and the manner in which these mechanisms break down in autism. The ongoing studies should therefore increase the understanding of the biological alterations associated with autism as well as the development of knowledge-based treatments therapy for those struggling with autism. In this review, we have presented recent advances in research based on animal models of autism, raising hope for understanding the disease biology for potential therapeutic intervention to improve the quality of life of autism individuals.
to be the prime model of inherited human disease and share 99% of their ... disturbances (including anxiety and depression) ..... Leibovici M, Safieddine S, Petit C (2008). Mouse models for human hereditary deafness. Curr. Top. Dev. Biol. 84:385-429. Levi YF, Meiner Z, Canello T, Frid K, Kovacs GG, Budka H, Avrahami.
Full Text Available Alzheimer's disease (AD is a degenerative disease of the central nervous system, and its pathogenesis is complex. Animal models play an important role in study on pathogenesis and treatment of AD. This paper summarized methods of building models, observation on animal models and evaluation index in recent years, so as to provide related evidence for basic and clinical research in future. DOI: 10.3969/j.issn.1672-6731.2015.08.003
Daetwyler, H.D.; Calus, M.P.L.; Pong-Wong, R.; Los Campos, De G.; Hickey, J.M.
The genomic prediction of phenotypes and breeding values in animals and plants has developed rapidly into its own research field. Results of genomic prediction studies are often difficult to compare because data simulation varies, real or simulated data are not fully described, and not all relevant
Armfield Jason M
Full Text Available Abstract Background The Cognitive Vulnerability Model holds that both clinical and sub-clinical manifestations of animal fears are a result of how an animal is perceived, and can be used to explain both individual differences in fear acquisition and the uneven distribution of fears in the population. This study looked at the association between fear of a number of animals and perceptions of the animals as uncontrollable, unpredictable, dangerous and disgusting. Also assessed were the perceived loomingness, prior familiarity, and negative evaluation of the animals as well as possible conditioning experiences. Methods 162 first-year University students rated their fear and perceptions of four high-fear and four low-fear animals. Results Perceptions of the animals as dangerous, disgusting and uncontrollable were significantly associated with fear of both high- and low-fear animals while perceptions of unpredictability were significantly associated with fear of high-fear animals. Conditioning experiences were unrelated to fear of any animals. In multiple regression analyses, loomingness did not account for a significant amount of the variance in fear beyond that accounted for by the cognitive vulnerability variables. However, the vulnerability variables accounted for between 20% and 51% of the variance in all animals fears beyond that accounted for by perceptions of the animals as looming. Perceptions of dangerousness, uncontrollability and unpredictability were highly predictive of the uneven distribution of animal fears. Conclusion This study provides support for the Cognitive Vulnerability Model of the etiology of specific fears and phobias and brings into question the utility of the harm-looming model in explaining animal fear.
Nicole Leite Galvão-Coelho
Full Text Available Major depression is a psychiatric disorder with high prevalence in the general population, with increasing expression in adolescence, about 14% in young people. Frequently, it presents as a chronic condition, showing no remission even after several pharmacological treatments and persisting in adult life. Therefore, distinct protocols and animal models have been developed to increase the understanding of this disease or search for new therapies. To this end, this study investigated the effects of chronic social isolation and the potential antidepressant action of nortriptyline in juvenile Callithrix jacchus males and females by monitoring fecal cortisol, body weight, and behavioral parameters and searching for biomarkers and a protocol for inducing depression. The purpose was to validate this species and protocol as a translational model of juvenile depression, addressing all domain criteria of validation: etiologic, face, functional, predictive, inter-relational, evolutionary, and population. In both sexes and both protocols (IDS and DPT, we observed a significant reduction in cortisol levels in the last phase of social isolation, concomitant with increases in autogrooming, stereotyped and anxiety behaviors, and the presence of anhedonia. The alterations induced by chronic social isolation are characteristic of the depressive state in non-human primates and/or in humans, and were reversed in large part by treatment with an antidepressant drug (nortriptyline. Therefore, these results indicate C. jacchus as a potential translational model of juvenile depression by addressing all criteria of validation.
Goldani, Luciano Z; Wirth, Fernanda
Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America. The morbidity and mortality associated with paracoccidioidomycosis necessitate our understanding of fungal pathogenesis and discovering of new agents to treat this infection. Animal models have contributed much to the knowledge of fungal infections and their corresponding therapeutic treatments. This is true for animal models of the primary fungal pathogens such as P. brasiliensis. This review describes the development, details and utility of animal models of paracoccidioidomycosis for studying and developing the current antifungal agents used for therapy of this fungal disease and novel agents with antifungal properties against P. brasiliensis.
Kantarci, Alpdogan; Hasturk, Hatice; Van Dyke, Thomas E
Translation of experimental data to the clinical setting requires the safety and efficacy of such data to be confirmed in animal systems before application in humans. In dental research, the animal species used is dependent largely on the research question or on the disease model. Periodontal disease and, by analogy, peri-implant disease, are complex infections that result in a tissue-degrading inflammatory response. It is impossible to explore the complex pathogenesis of periodontitis or peri-implantitis using only reductionist in-vitro methods. Both the disease process and healing of the periodontal and peri-implant tissues can be studied in animals. Regeneration (after periodontal surgery), in response to various biologic materials with potential for tissue engineering, is a continuous process involving various types of tissue, including epithelia, connective tissues and alveolar bone. The same principles apply to peri-implant healing. Given the complexity of the biology, animal models are necessary and serve as the standard for successful translation of regenerative materials and dental implants to the clinical setting. Smaller species of animal are more convenient for disease-associated research, whereas larger animals are more appropriate for studies that target tissue healing as the anatomy of larger animals more closely resembles human dento-alveolar architecture. This review focuses on the animal models available for the study of regeneration in periodontal research and implantology; the advantages and disadvantages of each animal model; the interpretation of data acquired; and future perspectives of animal research, with a discussion of possible nonanimal alternatives. Power calculations in such studies are crucial in order to use a sample size that is large enough to generate statistically useful data, whilst, at the same time, small enough to prevent the unnecessary use of animals. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Song, Yagang; Miao, Mingsan
Drug safety is a key factor in drug research and development, Drug toxicology test is the main method to evaluate the safety of drugs, The body condition of an animal has important implications for the results of the study, Previous toxicological studies of drugs were carried out in normal animals in the past, There is a great deviation from the clinical practice.The purpose of this study is to investigate the necessity of model animals as a substitute for normal animals for toxicological studies, It is expected to provide exact guidance for future drug safety evaluation.
Fernández-Borges, Natalia; Elezgarai, Saioa R; Eraña, Hasier; Castilla, Joaquín
Prion diseases belong to a group of fatal infectious diseases with no effective therapies available. Throughout the last 35 years, less than 50 different drugs have been tested in different experimental animal models without hopeful results. An important limitation when searching for new drugs is the existence of appropriate models of the disease. The three different possible origins of prion diseases require the existence of different animal models for testing anti-prion compounds. Wild type, over-expressing transgenic mice and other more sophisticated animal models have been used to evaluate a diversity of compounds which some of them were previously tested in different in vitro experimental models. The complexity of prion diseases will require more pre-screening studies, reliable sporadic (or spontaneous) animal models and accurate chemical modifications of the selected compounds before having an effective therapy against human prion diseases. This review is intended to put on display the more relevant animal models that have been used in the search of new antiprion therapies and describe some possible procedures when handling chemical compounds presumed to have anti-prion activity prior to testing them in animal models.
El-Shanshoury, H.; El-Shanshoury, G.; Abaza, A.
Exposure to ionizing radiation is known to have lethal effects in blood cells. It is predicted that an individual may spend days, weeks or even months in a radiation field without becoming alarmed. The study aimed to discuss the evaluation of low dose ionizing radiation (IR) effect on some blood components in animal model. Hematological parameters were determined for 110 animal rats (divided into 8 groups) pre- and post-irradiation. An attempt to explain the blood changes resulting from both ...
Full Text Available Medulloblastoma is a primary brain tumor found in the cerebellum of children. The tumor occurs in association with two inherited cancer syndromes: Turcot syndrome and Gorlin syndrome. Insights into the molecular biology of the tumor have come from looking at alterations in the genes altered in these syndromes, PTC and APC, respectively. Murine models of medulloblastoma have been constructed based on these alterations. Additional murine models that, while mimicking the appearance of the human tumor, seem unrelated to the human tumor's molecular alterations have been made. In this review, the clinical picture, origin, molecular biology, murine models of medulloblastoma are discussed. Although a great deal has been discovered about this tumor, the genetic alterations responsible for tumor development in a majority of patients have yet to be described.
Haiganoush K. Preisler; Alan A. Ager; Bruce K. Johnson; John G. Kie
We describe the use of bivariate stochastic differential equations (SDE) for modeling movements of 216 radiocollared female Rocky Mountain elk at the Starkey Experimental Forest and Range in northeastern Oregon. Spatially and temporally explicit vector fields were estimated using approximating difference equations and nonparametric regression techniques. Estimated...
Lynch, Wendy J; Nicholson, Katherine L; Dance, Mario E; Morgan, Richard W; Foley, Patricia L
Substance abuse and addiction are well recognized public health concerns, with 2 NIH institutes (the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism) specifically targeting this societal problem. As such, this is an important area of research for which animal experiments play a critical role. This overview presents the importance of substance abuse and addiction in society; reviews the development and refinement of animal models that address crucial areas of biology, pathophysiology, clinical treatments, and drug screening for abuse liability; and discusses some of the unique veterinary, husbandry, and IACUC challenges associated with these models.
Skuterud, L.; Strand, P. [Norwegian Radiation Protection Authority (Norway); Howard, B.J. [Inst. of Terrestrial Ecology (United Kingdom)
The radionuclides of most concern with respect to contamination of animals after a nuclear accident are radioiodine, radiocaesium and radiostrontium (ICRP 30, 1979). Of the other significant anthropogenic radionuclides likely to be released in most accidents, only small proportions of that ingested will be absorbed in an animals gut, and the main animal products, milk and meat, will not normally be contaminated to a significant extent. Animal products will mostly be contaminated as a result of ingestion of contaminated feed and possibly, but to a much lesser extent, from inhalation (for radioiodine only). Direct external contamination of animals is of little or no consequence in human food production. Radioiodine and radiostrontium are important with respect to contamination of milk; radiocaesium contaminates both milk and meat. The physical and chemical form of a radionuclide can influence its absorption in the animal gut. For example, following the Chernobyl accident radiocaesium incorporated into vegetation by root uptake was more readily absorbed than that associated with the original deposit. The transfer of radiocaesium and radiostrontium to animals will be presented both as transfer coefficients and aggregated transfer coefficients. For most animal meat products, only radiocaesium is important as other radionuclides do not significantly contaminate muscle. Farm animal products are the most important foodstuff determining radiocaesium intake by the average consumer in the Nordic countries. The major potential source of radioiodine and radiostrontium to humans is milk and milk products. Of the different species, the smaller animals have the highest transfer of radiocaesium from fodder to meat and milk. (EG). 68 refs.
Full Text Available Hepatitis B virus (HBV infection seriously affects human health. Stable and reliable animal models of HBV infection bear significance in studying pathogenesis of this health condition and development of intervention measures. HBV exhibits high specificity for hosts, and chimpanzee is long used as sole animal model of HBV infection. However, use of chimpanzees is strictly constrained because of ethical reasons. Many methods were used to establish small-animal models of HBV infection. Tupaia is the only nonprimate animal that can be infected by HBV. Use of HBV-related duck hepatitis virus and marmot hepatitis virus infection model contributed to evaluation of mechanism of HBV replication and HBV treatment methods. In recent years, development of human–mouse chimeric model provided possibility of using common experimental animals to carry out HBV research. These models feature their own advantages and disadvantages and can be complementary in some ways. This study provides an overview of current and commonly used animal models of HBV infection.
Harloff-Helleberg, Stine; Nielsen, Line Hagner; Nielsen, Hanne Mørck
of systems for oral delivery of biopharmaceuticals may result in new treatment modalities to increase the patient compliance and reduce product cost. In the preclinical development phase, use of experimental animal models is essential for evaluation of new formulation designs. In general, the limited oral...... bioavailability of biopharmaceuticals, of just a few percent, is expected, and therefore, the animal models and the experimental settings must be chosen with utmost care. More knowledge and focus on this topic is highly needed, despite experience from the numerous studies evaluating animal models for oral drug...... delivery of small molecule drugs. This review highlights and discusses pros and cons of the most currently used animal models and settings. Additionally, it also looks into the influence of anesthetics and sampling methods for evaluation of drug delivery systems for oral delivery of biopharmaceuticals...
D.L. Traber (Daniel); C.-C. Chen (Chien-Cheng); Y.-Y. Huang (Ying-Yu); M. Spoor (Monique); J. Roos (Jeanine); M.A. Frens (Maarten); D. Straumann (Dominik); C. Grimm (Christian)
textabstractPURPOSE. Individuals with oculocutaneous albinism are predisposed to visual system abnormalities affecting the retina and retinofugal projections, which may lead to reduced visual acuity and Infantile Nystagmus Syndrome (INS). Due to absence of an established mammalian animal model,
Full Text Available Experimental animal models offer possibilities of physiology knowledge, pathogenesis of disease and action of drugs that are directly related to quality nursing care. This integrative review describes the current state of the instrumental and ethical aspects of experimental research with animal models, including the main recommendations of ethics committees that focus on animal welfare and raises questions about the impact of their findings in nursing care. Data show that, in Brazil, the progress in ethics for the use of animals for scientific purposes was consolidated with Law No. 11.794/2008 establishing ethical procedures, attending health, genetic and experimental parameters. The application of ethics in handling of animals for scientific and educational purposes and obtaining consistent and quality data brings unquestionable contributions to the nurse, as they offer subsidies to relate pathophysiological mechanisms and the clinical aspect on the patient.
problems, including diabetes, cardiovascular disease, respiratory failure, muscle weakness, and cancer. The precise molecular mechanisms by which obesity induces these health problems are not yet clear. To better understand the pathomechanisms of human disease, good animal models are essential. In this paper, we will analyze animal models of obesity and their use in the research of obesity-associated human health conditions and diseases such as diabetes, cancer, and obstructive sleep apnea syndrome.
The de facto official source on facial animation—now updated!. If you want to do character facial modeling and animation at the high levels achieved in today's films and games, Stop Staring: Facial Modeling and Animation Done Right, Third Edition , is for you. While thoroughly covering the basics such as squash and stretch, lip syncs, and much more, this new edition has been thoroughly updated to capture the very newest professional design techniques, as well as changes in software, including using Python to automate tasks.: Shows you how to create facial animation for movies, games, and more;
Damgaard, Lars Holm
This paper deals with Bayesian inferences of animal models using Gibbs sampling. First, we suggest a general and efficient method for updating additive genetic effects, in which the computational cost is independent of the pedigree depth and increases linearly only with the size of the pedigree. ...... having Student's t distributions. In conclusion, Winbugs can be used to make inferences in small-sized, quantitative, genetic data sets applying a wide range of animal models that are not yet standard in the animal breeding literature...
Hanks, Ephraim M.; Johnson, Devin S.; Hooten, Mevin B.
Movement for many animal species is constrained in space by barriers such as rivers, shorelines, or impassable cliffs. We develop an approach for modeling animal movement constrained in space by considering a class of constrained stochastic processes, reflected stochastic differential equations. Our approach generalizes existing methods for modeling unconstrained animal movement. We present methods for simulation and inference based on augmenting the constrained movement path with a latent unconstrained path and illustrate this augmentation with a simulation example and an analysis of telemetry data from a Steller sea lion (Eumatopias jubatus) in southeast Alaska.
Ceciliani, Fabrizio; Restelli, Laura; Lecchi, Cristina
The need to provide in vivo complex environments to understand human diseases strongly relies on the use of animal models, which traditionally include small rodents and rabbits. It is becoming increasingly evident that the few species utilised to date cannot be regarded as universal. There is a great need for new animal species that are naturally endowed with specific features relevant to human diseases. Farm animals, including pigs, cows, sheep and horses, represent a valid alternative to commonly utilised rodent models. There is an ample scope for the application of proteomic techniques in farm animals, and the establishment of several proteomic maps of plasma and tissue has clearly demonstrated that farm animals provide a disease environment that closely resembles that of human diseases. The present review offers a snapshot of how proteomic techniques have been applied to farm animals to improve their use as biomedical models. Focus will be on specific topics of biomedical research in which farm animal models have been characterised through the application of proteomic techniques. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Kapischke, Matthias; Pries, Alexandra
The operative and conservative results of therapy in pancreatic ductal adenocarcinoma remain appallingly poor. This underlines the demand for further research for effective anticancer drugs. The various animal models remain the essential method for the determination of efficacy of substances during preclinical phase. Unfortunately, most of these tested substances showed a good efficacy in pancreatic carcinoma in the animal model but were not confirmed during the clinical phase. The available literature in PubMed, Medline, Ovid and secondary literature was searched regarding the available animal models for drug testing against pancreatic cancer. The models were analyzed regarding their pros and cons in anticancer drug testing. The different modifications of the orthotopic model (especially in mice) seem at present to be the best model for anticancer testing in pancreatic carcinoma. The value of genetically engineered animal model (GEM) and syngeneic models is on debate. A good selection of the model concerning the questions supposed to be clarified may improve the comparability of the results of animal experiments compared to clinical trials.
Lysgaard Poulsen, J; Stubbe, J; Lindholt, J S
OBJECTIVE: Experimental animal models have been used to investigate the formation, development, and progression of abdominal aortic aneurysms (AAAs) for decades. New models are constantly being developed to imitate the mechanisms of human AAAs and to identify treatments that are less risky than...... those used today. However, to the authors' knowledge, there is no model identical to the human AAA. The objective of this systematic review was to assess the different types of animal models used to investigate the development, progression, and treatment of AAA and to highlight their advantages...... and limitations. METHODS: A search protocol was used to perform a systematic literature search of PubMed and Embase. A total of 2,830 records were identified. After selection of the relevant articles, 564 papers on animal AAA models were included. RESULTS: The most common models in rodents, including elastase...
Gillian M. Lavelle
Full Text Available Cystic fibrosis (CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR gene. The resultant characteristic ion transport defect results in decreased mucociliary clearance, bacterial colonisation, and chronic neutrophil-dominated inflammation. Much knowledge surrounding the pathophysiology of the disease has been gained through the generation of animal models, despite inherent limitations in each. The failure of certain mouse models to recapitulate the phenotypic manifestations of human disease has initiated the generation of larger animals in which to study CF, including the pig and the ferret. This review will summarise the basic phenotypes of three animal models and describe the contributions of such animal studies to our current understanding of CF.
McGregor, Alistair; Choi, K. Yeon
Introduction Cytomegalovirus (CMV) is a ubiquitous pathogen that establishes a life long asymptomatic infection in healthy individuals. Infection of immunesuppressed individuals causes serious illness. Transplant and AIDS patients are highly susceptible to CMV leading to life threatening end organ disease. Another vulnerable population is the developing fetus in utero, where congenital infection can result in surviving newborns with long term developmental problems. There is no vaccine licensed for CMV and current antivirals suffer from complications associated with prolonged treatment. These include drug toxicity and emergence of resistant strains. There is an obvious need for new antivirals. Candidate intervention strategies are tested in controlled pre-clinical animal models but species specificity of HCMV precludes the direct study of the virus in an animal model. Areas covered This review explores the current status of CMV antivirals and development of new drugs. This includes the use of animal models and the development of new improved models such as humanized animal CMV and bioluminescent imaging of virus in animals in real time. Expert Opinion Various new CMV antivirals are in development, some with greater spectrum of activity against other viruses. Although the greatest need is in the setting of transplant patients there remains an unmet need for a safe antiviral strategy against congenital CMV. This is especially important since an effective CMV vaccine remains an elusive goal. In this capacity greater emphasis should be placed on suitable pre-clinical animal models and greater collaboration between industry and academia. PMID:21883024
Jessica K. Simmons
Full Text Available Prostate cancer bone metastases are associated with a poor prognosis and are considered incurable. Insight into the formation and growth of prostate cancer bone metastasis is required for development of new imaging and therapeutic strategies to combat this devastating disease. Animal models are indispensable in investigating cancer pathogenesis and evaluating therapeutics. Multiple animal models of prostate cancer bone metastasis have been developed, but few effectively model prostatic neoplasms and osteoblastic bone metastases as they occur in men. This review discusses the animal models that have been developed to investigate prostate cancer bone metastasis, with a focus on canine models and also includes human xenograft and rodent models. Adult dogs spontaneously develop benign prostatic hyperplasia and prostate cancer with osteoblastic bone metastases. Large animal models, such as dogs, are needed to develop new molecular imaging tools and effective focal intraprostatic therapy. None of the available models fully reflect the metastatic disease seen in men, although the various models have provided important insight into the metastatic process. As additional models are developed and knowledge from the different models is combined, the molecular mechanisms of prostate cancer bone metastasis can be deciphered and targeted for development of novel therapies and molecular diagnostic imaging.
Kokras, N; Dalla, C
Psychiatric disorders are characterized by sex differences in their prevalence, symptomatology and treatment response. Animal models have been widely employed for the investigation of the neurobiology of such disorders and the discovery of new treatments. However, mostly male animals have been used in preclinical pharmacological studies. In this review, we highlight the need for the inclusion of both male and female animals in experimental studies aiming at gender-oriented prevention, diagnosis and treatment of psychiatric disorders. We present behavioural findings on sex differences from animal models of depression, anxiety, post-traumatic stress disorder, substance-related disorders, obsessive–compulsive disorder, schizophrenia, bipolar disorder and autism. Moreover, when available, we include studies conducted across different stages of the oestrous cycle. By inspection of the relevant literature, it is obvious that robust sex differences exist in models of all psychiatric disorders. However, many times results are conflicting, and no clear conclusion regarding the direction of sex differences and the effect of the oestrous cycle is drawn. Moreover, there is a lack of considerable amount of studies using psychiatric drugs in both male and female animals, in order to evaluate the differential response between the two sexes. Notably, while in most cases animal models successfully mimic drug response in both sexes, test parameters and treatment-sensitive behavioural indices are not always the same for male and female rodents. Thus, there is an increasing need to validate animal models for both sexes and use standard procedures across different laboratories. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24697577
Full Text Available Even with an effective vaccine, an estimated 240 million people are chronically infected with hepatitis B virus (HBV worldwide. Current antiviral therapies, including interferon and nucleot(side analogues, rarely cure chronic hepatitis B. Animal models are very crucial for understanding the pathogenesis of chronic hepatitis B and developing new therapeutic drugs or strategies. HBV can only infect humans and chimpanzees, with the use of chimpanzees in HBV research strongly restricted. Thus, most advances in HBV research have been gained using mouse models with HBV replication or infection or models with HBV-related hepadnaviral infection. This review summarizes the animal models currently available for the study of HBV infection.
Full Text Available A variety of animal models have been suggested as models of pulmonary emphysema; these are critically discussed in the present article from a stereologist's perspective. In addition, a stereological design for the quantification of experimentally induced emphysema is proposed. On the basis of the widely accepted definition of pulmonary emphysema being an "abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls," quantitative morphology is the only method with which to reliably assess the presence of emphysema. Recognising this, careful inspection of animal models that are based on instillation of elastase, genetic alterations, inhalation of cigarette smoke or induction of apoptosis, reveals that both criteria of emphysema definition were demonstrated in surprisingly few of them. Several aspects are suggested to be critical for the understanding of animal models of human emphysema. For example, genetic models that rely on the inhibition of the formation of alveoli during post-natal alveolarisation should clearly be distinguished from models that rely on the loss of mature alveoli after alveolarisation is complete. Furthermore, inhalation models that are characterised by exposed animals exhibiting a severe loss of body weight should carefully examine the relative contribution of intervention and weight loss, respectively. Models that rely on the exposure of juvenile animals for several weeks or even months should take into account the effects of normal lung growth and ageing. Stereology offers appropriate tools with which to quantify the parameters relevant to assess development and the regeneration of emphysema. Stereologists continue to develop tools that will help ascertain the reliability of established and new models. If inappropriate parameters continue to be used for the evaluation of animal models of emphysema, thinking and resources are likely to be misdirected and the
Kalpesh Chhotalal Ashara
Full Text Available Models of animal are the most appropriate method for assessments of human in-vivo percutaneous and ocular penetrations. Monkey and rodents are used for the same. There are several nuts and bolts of each one, so it is necessary to study each one separately. Monkey, porcine and guinea pig penetration are correlated with that of human skin. The skin of rodents, lupus, pigs, etc. has more penetration properties than human skin. Rabbit, goat and sheep eye are mostly used for ocular penetration. The researcher also used hen’s egg chorioallantoic membrane test for ocular irritation study. The other animals’ cornea, cul-de-sac, eyeballs and prepared corneal epithelial models are very less in practice. Web-based alternative non-animal models are also available instead of animal models too. This article describes characteristics of monkeys, pigs, rats, rabbits, guinea pigs and hairless rodents, HuSki model, Cellophane® membrane, egg membrane, gelatin membrane, animal models for ophthalmic delivery, hen’s egg chorioallantoic membrane test, prepared corneal epithelial models and web-based alternative non-animal database.
Woods, H. Arthur; Smith, Jennifer N.
For terrestrial animals and plants, a fundamental cost of living is water vapor lost to the atmosphere during exchange of metabolic gases. Here, by bringing together previously developed models for specific taxa, we integrate properties common to all terrestrial gas exchangers into a universal model of water loss. The model predicts that water loss scales to gas exchange with an exponent of 1 and that the amount of water lost per unit of gas exchanged depends on several factors: the surface t...
Clarke, Iain J
Most laboratory-based research on obesity is carried out in rodents, but there are a number of other interesting models in the animal kingdom that are instructive. This includes domesticated animal species such as pigs and sheep, as well as wild, migrating and hibernating species. Larger animals allow particular experimental manipulations that are not possible in smaller animals and especially useful models have been developed to address issues such as manipulation of fetal development. Although some of the most well-studied models are ruminants, with metabolic control that differs from monogastrics, the general principles of metabolic regulation still pertain. It is possible to obtain much more accurate endocrine profiles in larger animals and this has provided important data in relation to leptin and ghrelin physiology. Genetic models have been created in domesticated animals through selection and these complement those of the laboratory rodent. This short review highlights particular areas of research in domesticated and wild species that expand our knowledge of systems that are important for our understanding of obesity and metabolism.
Modi, Meera E.; Young, Larry J.
Animal models and behavioral paradigms are critical for elucidating the neural mechanism involved in complex behaviors, including social cognition. Both genotype and phenotype based models have implicated the neuropeptide oxytocin (OT) in the regulation of social behavior. Based on the findings in animal models, alteration of the OT system has been hypothesized to play a role in the social deficits associated with autism and other neuropsychiatric disorders. While the evidence linking the peptide to the etiology of the disorder is not yet conclusive, evidence from multiple animal models suggest modulation of the OT system may be a viable strategy for the pharmacological treatment of social deficits. In this review, we will discuss how animal models have been utilized to understand the role of OT in social cognition and how those findings can be applied to the conceptualization and treatment of the social impairments in ASD. Animal models with genetic alterations of the OT system, like the OT, OT receptor and CD38 knock-out mice, and those with phenotypic variation in social behavior, like BTBR inbred mice and prairie voles, coupled with behavioral paradigms with face and construct validity may prove to have predictive validity for identifying the most efficacious methods of stimulating the OT system to enhance social cognition in humans. The widespread use of strong animal models of social cognition has the potential yield pharmacological, interventions for the treatment social impairments psychiatric disorders. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. PMID:22206823
Panzacchi, Manuela; Van Moorter, Bram; Strand, Olav; Saerens, Marco; Kivimäki, Ilkka; St Clair, Colleen C; Herfindal, Ivar; Boitani, Luigi
The loss, fragmentation and degradation of habitat everywhere on Earth prompts increasing attention to identifying landscape features that support animal movement (corridors) or impedes it (barriers). Most algorithms used to predict corridors assume that animals move through preferred habitat either optimally (e.g. least cost path) or as random walkers (e.g. current models), but neither extreme is realistic. We propose that corridors and barriers are two sides of the same coin and that animals experience landscapes as spatiotemporally dynamic corridor-barrier continua connecting (separating) functional areas where individuals fulfil specific ecological processes. Based on this conceptual framework, we propose a novel methodological approach that uses high-resolution individual-based movement data to predict corridor-barrier continua with increased realism. Our approach consists of two innovations. First, we use step selection functions (SSF) to predict friction maps quantifying corridor-barrier continua for tactical steps between consecutive locations. Secondly, we introduce to movement ecology the randomized shortest path algorithm (RSP) which operates on friction maps to predict the corridor-barrier continuum for strategic movements between functional areas. By modulating the parameter Ѳ, which controls the trade-off between exploration and optimal exploitation of the environment, RSP bridges the gap between algorithms assuming optimal movements (when Ѳ approaches infinity, RSP is equivalent to LCP) or random walk (when Ѳ → 0, RSP → current models). Using this approach, we identify migration corridors for GPS-monitored wild reindeer (Rangifer t. tarandus) in Norway. We demonstrate that reindeer movement is best predicted by an intermediate value of Ѳ, indicative of a movement trade-off between optimization and exploration. Model calibration allows identification of a corridor-barrier continuum that closely fits empirical data and demonstrates that RSP
Mittwede, Peter N; Clemmer, John S; Bergin, Patrick F; Xiang, Lusha
Critical illness is a major cause of morbidity and mortality around the world. While obesity is often detrimental in the context of trauma, it is paradoxically associated with improved outcomes in some septic patients. The reasons for these disparate outcomes are not well understood. A number of animal models have been used to study the obese response to various forms of critical illness. Just as there have been many animal models that have attempted to mimic clinical conditions, there are many clinical scenarios that can occur in the highly heterogeneous critically ill patient population that occupies hospitals and intensive care units. This poses a formidable challenge for clinicians and researchers attempting to understand the mechanisms of disease and develop appropriate therapies and treatment algorithms for specific subsets of patients, including the obese. The development of new, and the modification of existing animal models, is important in order to bring effective treatments to a wide range of patients. Not only do experimental variables need to be matched as closely as possible to clinical scenarios, but animal models with pre-existing comorbid conditions need to be studied. This review briefly summarizes animal models of hemorrhage, blunt trauma, traumatic brain injury, and sepsis. It also discusses what has been learned through the use of obese models to study the pathophysiology of critical illness in light of what has been demonstrated in the clinical literature.
Glud, A. N.; Bech, J.; Tvilling, L.
and subcortical anatomical differences. NEW METHOD: We present a convenient method to make an MRI-visible skull fiducial for 3D MRI-based stereotaxic procedures in larger experimental animals. Plastic screws were filled with either copper-sulphate solution or MRI-visible paste from a commercially available......BACKGROUND: Stereotaxic neurosurgery in large animals is used widely in different sophisticated models, where precision is becoming more crucial as desired anatomical target regions are becoming smaller. Individually calculated coordinates are necessary in large animal models with cortical...... cranial head marker. The screw fiducials were inserted in the animal skulls and T1 weighted MRI was performed allowing identification of the inserted skull marker. RESULTS: Both types of fiducial markers were clearly visible on the MRÍs. This allows high precision in the stereotaxic space. COMPARISON...
Maduwage, Kalana P; Scorgie, Fiona E; Lincz, Lisa F; O'Leary, Margaret A; Isbister, Geoffrey K
Animal models are used to test toxic effects of snake venoms/toxins and the antivenom required to neutralise them. However, venoms that cause clinically relevant coagulopathy in humans may have differential effects in animals. We aimed to investigate the effect of different procoagulant snake venoms on various animal plasmas. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer levels were measured in seven animal plasmas (human, rabbit, cat, guinea pig, pig, cow and rat). In vitro clotting times were then used to calculate the effective concentration (EC50) in each plasma for four snake venoms with different procoagulant toxins: Pseudonaja textilis, Daboia russelli, Echis carinatus and Calloselasma rhodostoma. Compared to human, PT and aPTT were similar for rat, rabbit and pig, but double for cat and cow, while guinea pig had similar aPTT but double PT. Fibrinogen and D-dimer levels were similar for all species. Human and rabbit plasmas had the lowest EC50 for P. textilis (0.1 and 0.4 μg/ml), D. russelli (0.4 and 0.1 μg/ml), E. carinatus (0.6 and 0.1 μg/ml) venoms respectively, while cat plasma had the lowest EC50 for C. rhodostoma (11 μg/ml) venom. Cow, rat, pig and guinea pig plasmas were highly resistant to all four venoms with EC50 10-fold that of human. Different animal plasmas have varying susceptibility to procoagulant venoms, and excepting rabbits, animal models are not appropriate to test procoagulant activity. In vitro assays on human plasma should instead be adopted for this purpose. Copyright © 2015 Elsevier Ltd. All rights reserved.
Full Text Available In recent years, the incidence of nonalcoholic fatty liver disease (NAFLD has increased gradually along with the rising prevalence of obesity, type 2 diabetes, and hyperlipidemia, and NAFLD has become one of the most common chronic liver diseases in the world and the second major liver disease after chronic viral hepatitis in China. However, its pathogenesis has not yet been clarified. Animal models are playing an important role in researches on NAFLD due to the facts that the development and progression of NAFLD require a long period of time, and ethical limitations exist in conducting drug trials in patients or collecting liver tissues from patients. The animal models with histopathology similar to that of NAFLD patients are reviewed, and their modeling principle, as well as the advantages and disadvantages, are compared. Animal models provide a powerful tool for further studies of NAFLD pathogenesis and drug screening for prevention and treatment of NAFLD.
Full Text Available The Gram-negative bacillus Helicobacter pylori is widely recognized as a major etiologic agent responsible for chronic active gastritis, peptic ulcers, the development of gastric cancer and mucosa-associated lymphoid tissue (MALT lymphoma. Still, little is known about the natural history of H. pylori infection, since patients usually after many years of not suffering from symptoms of the infection are simply asymptomatic. Since the research investigators carried out on human models has many limitations, there is an urgent need for the development of an animal model optimal and suitable for the monitoring of H. pylori infections. This review summarizes the recent findings on the suitability of animal models used in H. pylori research. Several animal models are useful for the assessment of pathological, microbiological and immunological consequences of infection, which makes it possible to monitor the natural
Full Text Available IL-17-secreting helper CD4 T cells (Th17 cells constitute a newly identified subset of helper CD4 T cells that play a key role in the development of rheumatoid arthritis (RA in its animal models. Recently, several models of spontaneous RA, which elucidate the mechanism of RA onset, have been discovered. These animal models shed new light on the role of Th17 in the development of autoimmune arthritis. Th17 cells coordinate inflammation and promote joint destruction, acting on various cells, including neutrophils, macrophages, synovial fibroblasts, and osteoclasts. Regulatory T cells cannot control Th17 cells under conditions of inflammation. In this review, the pathogenic role of Th17 cells in arthritis development, which was revealed by the recent animal models of RA, is discussed.
IL-17-secreting helper CD4 T cells (Th17 cells) constitute a newly identified subset of helper CD4 T cells that play a key role in the development of rheumatoid arthritis (RA) in its animal models. Recently, several models of spontaneous RA, which elucidate the mechanism of RA onset, have been discovered. These animal models shed new light on the role of Th17 in the development of autoimmune arthritis. Th17 cells coordinate inflammation and promote joint destruction, acting on various cells, including neutrophils, macrophages, synovial fibroblasts, and osteoclasts. Regulatory T cells cannot control Th17 cells under conditions of inflammation. In this review, the pathogenic role of Th17 cells in arthritis development, which was revealed by the recent animal models of RA, is discussed.
Full Text Available Tuberculosis (TB is a health threat to the global population. Anti-TB drugs and vaccines are key approaches for TB prevention and control. TB animal models are basic tools for developing biomarkers of diagnosis, drugs for therapy, vaccines for prevention and researching pathogenic mechanisms for identification of targets; thus, they serve as the cornerstone of comparative medicine, translational medicine, and precision medicine. In this review, we discuss the current use of TB animal models and their problems, as well as offering perspectives on the future of these models.
Full Text Available Post-traumatic stress disorder (PTSD is a debilitating condition that develops in a proportion of individuals following a traumatic event. Despite recent advances, ethical limitations associated with human research impede progress in understanding PTSD. Fortunately, much effort has focused on developing animal models to help study the pathophysiology of PTSD. Here, we provide an overview of animal PTSD models where a variety of stressors (physical, psychosocial, or psychogenic are used to examine the long-term effects of severe trauma. We emphasize models involving predator threat because they reproduce human individual differences in susceptibility to, and in the long-term consequences of, psychological trauma.
Goswami, Sonal; Rodríguez-Sierra, Olga; Cascardi, Michele; Paré, Denis
Post-traumatic stress disorder (PTSD) is a debilitating condition that develops in a proportion of individuals following a traumatic event. Despite recent advances, ethical limitations associated with human research impede progress in understanding PTSD. Fortunately, much effort has focused on developing animal models to help study the pathophysiology of PTSD. Here, we provide an overview of animal PTSD models where a variety of stressors (physical, psychosocial, or psychogenic) are used to examine the long-term effects of severe trauma. We emphasize models involving predator threat because they reproduce human individual differences in susceptibility to, and in the long-term consequences of, psychological trauma. PMID:23754973
Zhan, Lingjun; Tang, Jun; Sun, Mengmeng; Qin, Chuan
Tuberculosis (TB) is a health threat to the global population. Anti-TB drugs and vaccines are key approaches for TB prevention and control. TB animal models are basic tools for developing biomarkers of diagnosis, drugs for therapy, vaccines for prevention and researching pathogenic mechanisms for identification of targets; thus, they serve as the cornerstone of comparative medicine, translational medicine, and precision medicine. In this review, we discuss the current use of TB animal models and their problems, as well as offering perspectives on the future of these models.
Marson, Lesley; Giamberardino, Maria Adele; Costantini, Raffaele; Czakanski, Peter; Wesselmann, Ursula
Introduction Significant progress has been made in elucidating the physiological and pharmacological mechanisms of female sexual function through preclinical animal research. The continued development of animal models is vital for the understanding and treatment of the many diverse disorders that occur in women. Aim To provide an updated review of the experimental models evaluating female sexual function that may be useful for clinical translation. Methods Review of English written, peer-reviewed literature, primarily from 2000 to 2012, that described studies on female sexual behavior related to motivation, arousal, physiological monitoring of genital function and urogenital pain. Main Outcomes Measures Analysis of supporting evidence for the suitability of the animal model to provide measurable indices related to desire, arousal, reward, orgasm, and pelvic pain. Results The development of female animal models has provided important insights in the peripheral and central processes regulating sexual function. Behavioral models of sexual desire, motivation, and reward are well developed. Central arousal and orgasmic responses are less well understood, compared with the physiological changes associated with genital arousal. Models of nociception are useful for replicating symptoms and identifying the neurobiological pathways involved. While in some cases translation to women correlates with the findings in animals, the requirement of circulating hormones for sexual receptivity in rodents and the multifactorial nature of women’s sexual function requires better designed studies and careful analysis. The current models have studied sexual dysfunction or pelvic pain in isolation; combining these aspects would help to elucidate interactions of the pathophysiology of pain and sexual dysfunction. Conclusions Basic research in animals has been vital for understanding the anatomy, neurobiology, and physiological mechanisms underlying sexual function and urogenital pain
Knippels, L.M.J.; Wijk, F. van; Penninks, A.H.
Purpose of review This review summarizes selected articles on animal models of food allergy published in 2003. The research areas that are covered include mechanistic studies, the search for new therapies, as well as screening models for hazard identification of potential allergens. Recent findings
The study of human genetic diseases can be greatly aided by animal models because of their similarity to humans in terms of genetics. In addition to understand diverse aspects of basic biology, model organisms are extensively used in applied research in agriculture, industry, and also in medicine, where they are used to ...
Rosenberg, J; Presch, I; Pommergaard, H C
pigs, and a total of 55 surgeons have been educated to perform Lichtenstein's hernia repair in these animals. CONCLUSIONS: This new experimental surgical model for training Lichtenstein's hernia repair mimics the human inguinal anatomy enough to make it suitable as a training model. The operation...
Szechtman, Henry; Ahmari, Susanne E; Beninger, Richard J; Eilam, David; Harvey, Brian H; Edemann-Callesen, Henriette; Winter, Christine
Research with animal models of obsessive-compulsive disorder (OCD) shows the following: (1) Optogenetic studies in mice provide evidence for a plausible cause-effect relation between increased activity in cortico-basal ganglia-thalamo-cortical (CBGTC) circuits and OCD by demonstrating the induction of compulsive behavior with the experimental manipulation of the CBGTC circuit. (2) Parallel use of several animal models is a fruitful paradigm to examine the mechanisms of treatment effects of deep brain stimulation in distinct OCD endophenotypes. (3) Features of spontaneous behavior in deer mice constitute a rich platform to investigate the neurobiology of OCD, social ramifications of a compulsive phenotype, and test novel drugs. (4) Studies in animal models for psychiatric disorders comorbid with OCD suggest comorbidity may involve shared neural circuits controlling expression of compulsive behavior. (5) Analysis of compulsive behavior into its constitutive components provides evidence from an animal model for a motivational perspective on OCD. (6) Methods of behavioral analysis in an animal model translate to dissection of compulsive rituals in OCD patients, leading to diagnostic tests. Copyright © 2016 Elsevier Ltd. All rights reserved.
Solevåg, Anne Lee; Cheung, Po-Yin; Lie, Helene; O'Reilly, Megan; Aziz, Khalid; Nakstad, Britt; Schmölzer, Georg Marcus
Much of the knowledge about the optimal way to perform chest compressions (CC) in newborn infants is derived from animal studies. The objective of this review was to identify studies of CC in newborn term animal models and review the evidence. We also provide an overview of the different models. MEDLINE, EMBASE and CINAHL, until September 29th 2014. Study eligibility criteria and interventions: term newborn animal models where CC was performed. Based on 419 retrieved studies from MEDLINE and 502 from EMBASE, 28 studies were included. No additional studies were identified in CINAHL. Most of the studies were performed in pigs after perinatal transition without long-term follow-up. The models differed widely in methodological aspects, which limits the possibility to compare and synthesize findings. Studies uncommonly reported the method for randomization and allocation concealment, and a limited number were blinded. Only the evidence in favour of the two-thumb encircling hands technique for performing CC, a CC to ventilation ratio of 3:1; and that air can be used for ventilation during CC; was supported by more than one study. Animal studies should be performed and reported with the same rigor as in human randomized trials. Good transitional and survival models are needed to further increase the strength of the evidence derived from animal studies of newborn chest compressions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Stevens, Hanna E; Vaccarino, Flora M
Every available approach should be used to advance the field of child and adolescent psychiatry. Biological systems are important for the behavioral problems of children. Close examination of nonhuman animals and the biology and behavior that they share with humans is an approach that must be used to advance the clinical work of child psychiatry. We review here how model systems are used to contribute to significant insights into childhood psychiatric disorders. Model systems have not only demonstrated causality of risk factors for psychiatric pathophysiology, but have also allowed child psychiatrists to think in different ways about risks for psychiatric disorders and multiple levels that might be the basis of recovery and prevention. We present examples of how animal systems are used to benefit child psychiatry, including through environmental, genetic, and acute biological manipulations. Animal model work has been essential in our current thinking about childhood disorders, including the importance of dose and timing of risk factors, specific features of risk factors that are significant, neurochemistry involved in brain functioning, molecular components of brain development, and the importance of cellular processes previously neglected in psychiatric theories. Animal models have clear advantages and disadvantages that must be considered for these systems to be useful. Coupled with increasingly sophisticated methods for investigating human behavior and biology, animal model systems will continue to make essential contributions to our field. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
Full Text Available Cheryl A Lawson,1,2 Douglas R Martin2,3 1Department of Pathobiology, 2Scott-Ritchey Research Center, 3Department of Anatomy, Physiology and Pharmacology, Auburn University College of Veterinary Medicine, Auburn, AL, USA Abstract: GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. Keywords: GM2 gangliosidosis, Tay–Sachs disease, Sandhoff disease, lysosomal storage disorder, sphingolipidosis, brain disease
Lawson, Cheryl A; Martin, Douglas R
GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay-Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay-Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described.
Bovenkerk, Bernice; Kaldewaij, Frederike
Animal models are used in experiments in the behavioural neurosciences that aim to contribute to the prevention and treatment of cognitive and affective disorders in human beings, such as anxiety and depression. Ironically, those animals that are likely to be the best models for psychopathology are also likely to be considered the ones that are most morally problematic to use, if it seems probable that (and if indeed they are initially selected as models because) they have experiences that are similar to human experiences that we have strong reasons to avoid causing, and indeed aim to alleviate (such as pain, anxiety or sadness). In this paper, against the background of contemporary discussions in animal ethics and the philosophy of animal minds, we discuss the views that it is morally permissible to use animals in these kinds of experiments, and that it is better to use less cognitively complex animals (such as zebrafish) than more complex animals (such as dogs). First, we criticise some justifications for the claim that human beings and more complex animals have higher moral status. We argue that contemporary approaches that attribute equal moral status to all beings that are capable of conscious strivings strivings (e.g. avoiding pain and anxiety; aiming to eat and play) are based on more plausible assumptions. Second, we argue that it is problematic to assume that less cognitively complex animals have a lesser sensory and emotional experience than more complex beings across the board. In specific cases, there might be good reasons to assume that more complex beings would be harmed more by a specific physical or environmental intervention, but it might also be that they sometimes are harmed less because of a better ability to cope. Determining whether a specific experiment is justified is therefore a complex issue. Our aim in this chapter is to stimulate further reflection on these common assumptions behind the use of animal models for psychopathologies. In
Jang, R.; Sung, M.; Hwang, J.; Jeon, S. W.
The Republic of Korea has undergone rapid development and urban development without sufficient consideration of the environment. This type of growth is accompanied by a reduction in forest area and wildlife habitat. It is a phenomenon that affects the habitat of large mammals more than small. Especially in Korea, the damage caused by wild boar(Sus scrofa) is harsher than other large mammalian species like water deer(Hydropotes inermis), which also means that the number of these reported cases of this species is higher than ones of other mammals. Wild boar has three to eight cubs per year and it is possible to breed every year, which makes it more populous comparing with the fragmented habitats. It could be regarded as one of the top predators in Korea, which it is inevitable for humans to intervene this creature in population control. In addition, some individuals have been forced to be retreated from other habitats in major habitats, or to invade human activity areas for food activity, thereby destroying crops. Ultimately, this mammal species has been treated as farm pest animals through committing road kills and urban emergences. In this study, we has estimated possible farm pest animal present points from the damage district using 2,505 hazardous wildlife damage areas with four types of geological informations, four kinds of forest information, land cover, and distribution of farmland occurred in Gyeongnam province in Korea. In the estimating model, utilizing MAXENT, information of background point was set to 10,000, 70% of the damaged sites were used to construct the model, 30% was used for verification, and 10 times of crossvalidate were proceeded - verified by AUC of ROC. As a result of analyses, AUC was 0.847, and the percent contribution of the forest information was the distance toward inner-forest areas, 36.1%, the land cover, 16.5%, the distance from the field, 14.9%. Furthermore, the permutation importance was 24.9% of the cover, 12.3% of the height
Hill, William G
Although animal breeding was practiced long before the science of genetics and the relevant disciplines of population and quantitative genetics were known, breeding programs have mainly relied on simply selecting and mating the best individuals on their own or relatives' performance. This is based on sound quantitative genetic principles, developed and expounded by Lush, who attributed much of his understanding to Wright, and formalized in Fisher's infinitesimal model. Analysis at the level of individual loci and gene frequency distributions has had relatively little impact. Now with access to genomic data, a revolution in which molecular information is being used to enhance response with "genomic selection" is occurring. The predictions of breeding value still utilize multiple loci throughout the genome and, indeed, are largely compatible with additive and specifically infinitesimal model assumptions. I discuss some of the history and genetic issues as applied to the science of livestock improvement, which has had and continues to have major spin-offs into ideas and applications in other areas.
Sloff, Marije; de Vries, Rob; Geutjes, Paul; IntHout, Joanna; Ritskes-Hoitinga, Merel
Tissue engineering and regenerative medicine (TERM) approaches may provide alternatives for gastrointestinal tissue in urinary diversion. To continue to clinically translatable studies, TERM alternatives need to be evaluated in (large) controlled and standardized animal studies. Here, we investigated all evidence for the efficacy of tissue engineered constructs in animal models for urinary diversion. Studies investigating this subject were identified through a systematic search of three different databases (PubMed, Embase and Web of Science). From each study, animal characteristics, study characteristics and experimental outcomes for meta-analyses were tabulated. Furthermore, the reporting of items vital for study replication was assessed. The retrieved studies (8 in total) showed extreme heterogeneity in study design, including animal models, biomaterials and type of urinary diversion. All studies were feasibility studies, indicating the novelty of this field. None of the studies included appropriate control groups, i.e. a comparison with the classical treatment using GI tissue. The meta-analysis showed a trend towards successful experimentation in larger animals although no specific animal species could be identified as the most suitable model. Larger animals appear to allow a better translation to the human situation, with respect to anatomy and surgical approaches. It was unclear whether the use of cells benefits the formation of a neo urinary conduit. The reporting of the methodology and data according to standardized guidelines was insufficient and should be improved to increase the value of such publications. In conclusion, animal models in the field of TERM for urinary diversion have probably been chosen for reasons other than their predictive value. Controlled and comparative long term animal studies, with adequate methodological reporting are needed to proceed to clinical translatable studies. This will aid in good quality research with the reduction in
Full Text Available Tissue engineering and regenerative medicine (TERM approaches may provide alternatives for gastrointestinal tissue in urinary diversion. To continue to clinically translatable studies, TERM alternatives need to be evaluated in (large controlled and standardized animal studies. Here, we investigated all evidence for the efficacy of tissue engineered constructs in animal models for urinary diversion. Studies investigating this subject were identified through a systematic search of three different databases (PubMed, Embase and Web of Science. From each study, animal characteristics, study characteristics and experimental outcomes for meta-analyses were tabulated. Furthermore, the reporting of items vital for study replication was assessed. The retrieved studies (8 in total showed extreme heterogeneity in study design, including animal models, biomaterials and type of urinary diversion. All studies were feasibility studies, indicating the novelty of this field. None of the studies included appropriate control groups, i.e. a comparison with the classical treatment using GI tissue. The meta-analysis showed a trend towards successful experimentation in larger animals although no specific animal species could be identified as the most suitable model. Larger animals appear to allow a better translation to the human situation, with respect to anatomy and surgical approaches. It was unclear whether the use of cells benefits the formation of a neo urinary conduit. The reporting of the methodology and data according to standardized guidelines was insufficient and should be improved to increase the value of such publications. In conclusion, animal models in the field of TERM for urinary diversion have probably been chosen for reasons other than their predictive value. Controlled and comparative long term animal studies, with adequate methodological reporting are needed to proceed to clinical translatable studies. This will aid in good quality research with
Burggren, Warren W; Warburton, Stephen
The concept of animal models is well honored, and amphibians have played a prominent part in the success of using key species to discover new information about all animals. As animal models, amphibians offer several advantages that include a well-understood basic physiology, a taxonomic diversity well suited to comparative studies, tolerance to temperature and oxygen variation, and a greater similarity to humans than many other currently popular animal models. Amphibians now account for approximately 1/4 to 1/3 of lower vertebrate and invertebrate research, and this proportion is especially true in physiological research, as evident from the high profile of amphibians as animal models in Nobel Prize research. Currently, amphibians play prominent roles in research in the physiology of musculoskeletal, cardiovascular, renal, respiratory, reproductive, and sensory systems. Amphibians are also used extensively in physiological studies aimed at generating new insights in evolutionary biology, especially in the investigation of the evolution of air breathing and terrestriality. Environmental physiology also utilizes amphibians, ranging from studies of cryoprotectants for tissue preservation to physiological reactions to hypergravity and space exploration. Amphibians are also playing a key role in studies of environmental endocrine disruptors that are having disproportionately large effects on amphibian populations and where specific species can serve as sentinel species for environmental pollution. Finally, amphibian genera such as Xenopus, a genus relatively well understood metabolically and physiologically, will continue to contribute increasingly in this new era of systems biology and "X-omics."
Rogers, Christopher S
Animal models are an important resource for studying human diseases. Genetically engineered mice are the most commonly used species and have made significant contributions to our understanding of basic biology, disease mechanisms, and drug development. However, they often fail to recreate important aspects of human diseases and thus can have limited utility as translational research tools. Developing disease models in species more similar to humans may provide a better setting in which to study disease pathogenesis and test new treatments. This unit provides an overview of the history of genetically engineered large animals and the techniques that have made their development possible. Factors to consider when planning a large animal model, including choice of species, type of modification and methodology, characterization, production methods, and regulatory compliance, are also covered. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.
Andrade, Ana Laura Martins de; Parisi, Julia Risso; Brassolatti, Patrícia; Parizotto, Nivaldo Antonio
To present an alternative experimental model of third degree burn of easy reproducibility. Eighteen male Wister rats were randomly divided into three groups, 6 of which were allocated to each group. A soldering iron coupled to an aluminum plate was used to produce burn, at a temperature of 150ºC, with different exposure times per group. Group 5 (G5) animals were burned at 150°C with exposure time of 5 seconds; Group 10 (G10) the animals were burned at 150°C with exposure time of 10 seconds and group 15 (G15) the animals were burned at 150°C with exposure time of 15 seconds. Histopathological analyzes showed that all three groups had similar morphological characteristics, with total thickness involvement. The technique is effective to reproduce a third degree burn and suggests the temperature of 150ºC with 5 seconds of exposure in order to minimize the risks to the animals.
Lo, Amy C. Y.
Diabetic retinopathy (DR) is a microvascular complication associated with chronic exposure to hyperglycemia and is a major cause of blindness worldwide. Although clinical assessment and retinal autopsy of diabetic patients provide information on the features and progression of DR, its underlying pathophysiological mechanism cannot be deduced. In order to have a better understanding of the development of DR at the molecular and cellular levels, a variety of animal models have been developed. They include pharmacological induction of hyperglycemia and spontaneous diabetic rodents as well as models of angiogenesis without diabetes (to compensate for the absence of proliferative DR symptoms). In this review, we summarize the existing protocols to induce diabetes using STZ. We also describe and compare the pathological presentations, in both morphological and functional aspects, of the currently available DR animal models. The advantages and disadvantages of using different animals, ranging from zebrafish, rodents to other higher-order mammals, are also discussed. Until now, there is no single model that displays all the clinical features of DR as seen in human. Yet, with the understanding of the pathological findings in these animal models, researchers can select the most suitable models for mechanistic studies or drug screening. PMID:24286086
Sun, Fu; Qu, Ji-Ning; Zhang, Yin-Gang
The establishment of a reliable animal model of lumbar disc degeneration (AMDD) is important for studying pathogenesis and evaluating treatment effectiveness. However, an ideal AMDD for use in laboratory studies has not yet been produced. This retrospective study reviews and compares several common AMDD and discusses their strengths and weaknesses. We also suggest a new method for establishing future AMDD. The identified genes associated with disc degeneration are susceptibility genes, which elevate risk but do not necessarily lead to disease occurrence. We propose to identify families with hereditary disc degeneration, find major casual genes with exome sequencing, and establish transgenic animal models. This approach may help us to build an improved AMDD.
Tyutyunov, Yuri V.; Titova, Lyudmila I.
Minimal mathematical models able to explain complex patterns of animal behavior are essential parts of simulation systems describing large-scale spatiotemporal dynamics of trophic communities, particularly those with wide-ranging species, such as occur in pelagic environments. We present results obtained with three different modelling approaches: (i) an individual-based model of animal spatial behavior; (ii) a continuous taxis-diffusion-reaction system of partial-difference equations; (iii) a 'hybrid' approach combining the individual-based algorithm of organism movements with explicit description of decay and diffusion of the movement stimuli. Though the models are based on extremely simple rules, they all allow description of spatial movements of animals in a predator-prey system within a closed habitat, reproducing some typical patterns of the pursuit-evasion behavior observed in natural populations. In all three models, at each spatial position the animal movements are determined by local conditions only, so the pattern of collective behavior emerges due to self-organization. The movement velocities of animals are proportional to the density gradients of specific cues emitted by individuals of the antagonistic species (pheromones, exometabolites or mechanical waves of the media, e.g., sound). These cues play a role of taxis stimuli: prey attract predators, while predators repel prey. Depending on the nature and the properties of the movement stimulus we propose using either a simplified individual-based model, a continuous taxis pursuit-evasion system, or a little more detailed 'hybrid' approach that combines simulation of the individual movements with the continuous model describing diffusion and decay of the stimuli in an explicit way. These can be used to improve movement models for many species, including large marine predators.
Hajishengallis, George; Lamont, Richard J; Graves, Dana T
Whereas no single animal model can reproduce the complexity of periodontitis, different aspects of the disease can be addressed by distinct models. Despite their limitations, animal models are essential for testing the biological significance of in vitro findings and for establishing cause-and-effect relationships relevant to clinical observations, which are typically correlative. We provide evidence that animal-based studies have generated a durable framework for dissecting the mechanistic basis of periodontitis. These studies have solidified the etiologic role of bacteria in initiating the inflammatory response that leads to periodontal bone loss and have identified key mediators (IL-1, TNF, prostaglandins, complement, RANKL) that induce inflammatory breakdown. Moreover, animal studies suggest that dysbiosis, rather than individual bacterial species, are important in initiating periodontal bone loss and have introduced the concept that organisms previously considered commensals can play important roles as accessory pathogens or pathobionts. These studies have also provided insight as to how systemic conditions, such as diabetes or leukocyte adhesion deficiency, contribute to tissue destruction. In addition, animal studies have identified and been useful in testing therapeutic targets.
Full Text Available Cardiovascular imaging has become an indispensable tool for patient diagnosis and follow up. Probably the wide clinical applications of imaging are due to the possibility of a detailed and high quality description and quantification of cardiovascular system structure and function. Also phenomena that involve complex physiological mechanisms and biochemical pathways, such as inflammation and ischemia, can be visualized in a nondestructive way. The widespread use and evolution of imaging would not have been possible without animal studies. Animal models have allowed for instance, i the technical development of different imaging tools, ii to test hypothesis generated from human studies and finally, iii to evaluate the translational relevance assessment of in vitro and ex-vivo results. In this review, we will critically describe the contribution of animal models to the use of biomedical imaging in cardiovascular medicine. We will discuss the characteristics of the most frequent models used in/for imaging studies. We will cover the major findings of animal studies focused in the cardiovascular use of the repeatedly used imaging techniques in clinical practice and experimental studies. We will also describe the physiological findings and/or learning processes for imaging applications coming from models of the most common cardiovascular diseases. In these diseases, imaging research using animals has allowed the study of aspects such as: ventricular size, shape, global function and wall thickening, local myocardial function, myocardial perfusion, metabolism and energetic assessment, infarct quantification, vascular lesion characterization, myocardial fiber structure, and myocardial calcium uptake. Finally we will discuss the limitations and future of imaging research with animal models.
Gopinath, Chitra; Nathar, Trupti Job; Ghosh, Arkasubhra; Hickstein, Dennis Durand; Nelson, Everette Jacob Remington
Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial.
This study aims to improve the accuracy of AASHTO Mechanistic-Empirical Pavement Design Guide (MEPDG) pavement : performance predictions for Iowa pavement systems through local calibration of MEPDG prediction models. A total of 130 : representative p...
Nanni, Cristina; Spinelli, Antonello; Trespidi, Silvia; Ambrosini, Valentina; Castellucci, Paolo; Farsad, Mohsen; Franchi, Roberto; Fanti, Stefano; Leo, Korinne di; Tonelli, Roberto; Pession, Andrea; Pettinato, Cinzia; Rubello, Domenico
The administration of new anticancer drugs in animal models is the first step from in vitro to in vivo pre-clinical protocols. At this stage it is crucial to ensure that cells are in the logarithmic phase of growth and to avoid vascular impairment, which can cause inhomogeneous distribution of the drug within the tumour and thus lead to bias in the final analysis of efficacy. In subcutaneous xenograft murine models, positivity for cancer is visually recognisable 2-3 weeks after inoculation, when a certain amount of necrosis is usually already present. The aim of this study was to evaluate the accuracy of FDG small animal PET for the early detection of malignant masses in a xenograft murine model of human rhabdomyosarcoma. A second goal was to analyse the metabolic behaviour of this xenograft tumour over time. We studied 23 nude mice, in which 7 x 10 6 rhabdomyosarcoma cells (RH-30 cell line) were injected in the dorsal subcutaneous tissues. Each animal underwent four FDG PET scans (GE, eXplore Vista DR) under gas anaesthesia. The animals were studied 2, 5, 14 and 20 days after inoculation. We administered 20 MBq of FDG via the tail vein. Uptake time was 60 min, and acquisition time, 20 min. Images were reconstructed with OSEM 2D iterative reconstruction and the target to background ratio (TBR) was calculated for each tumour. Normal subcutaneous tissue had a TBR of 0.3. Necrosis was diagnosed when one or more cold areas were present within the mass. All the animals were sacrificed and histology was available to verify PET results. PET results were concordant with the findings of necropsy and histology in all cases. The incidence of the tumour was 69.6% (16/23 animals); seven animals did not develop a malignant mass. Ten of the 23 animals had a positive PET scan 2 days after inoculation. Nine of these ten animals developed a tumour; the remaining animal became negative, at the third scan. The positive predictive value of the early PET scan was 90% (9/10 animals
Schoups, G.; Van de Giesen, N.C.; Savenije, H.H.G.
A common concern in hydrologic modeling is overparameterization of complex models given limited and noisy data. This leads to problems of parameter nonuniqueness and equifinality, which may negatively affect prediction uncertainties. A systematic way of controlling model complexity is therefore
A I Pearce
Full Text Available Development of an optimal interface between bone and orthopaedic and dental implants has taken place for many years. In order to determine whether a newly developed implant material conforms to the requirements of biocompatibility, mechanical stability and safety, it must undergo rigorous testing both in vitro and in vivo. Results from in vitro studies can be difficult to extrapolate to the in vivo situation. For this reason the use of animal models is often an essential step in the testing of orthopaedic and dental implants prior to clinical use in humans. This review discusses some of the more commonly available and frequently used animal models such as the dog, sheep, goat, pig and rabbit models for the evaluation of bone-implant interactions. Factors for consideration when choosing an animal model and implant design are discussed. Various bone specific features are discussed including the usage of the species, bone macrostructure and microstructure and bone composition and remodelling, with emphasis being placed on the similarity between the animal model and the human clinical situation. While the rabbit was the most commonly used of the species discussed in this review, it is clear that this species showed the least similarities to human bone. There were only minor differences in bone composition between the various species and humans. The pig demonstrated a good likeness with human bone however difficulties may be encountered in relation to their size and ease of handling. In this respect the dog and sheep/goat show more promise as animal models for the testing of bone implant materials. While no species fulfils all of the requirements of an ideal model, an understanding of the differences in bone architecture and remodelling between the species is likely to assist in the selection of a suitable species for a defined research question.
Studies on stress and its impacts on animals are very important in many fields of science, including animal science, because various stresses influence animal production and animal welfare. In particular, the social stresses within animal groups have profound impact on animals, with the potential to induce abnormal behaviors and health problems. In humans, social stress induces several health problems, including psychiatric disorders. In animal stress models, social defeat models are well characterized and used in various research fields, particularly in studies concerning mental disorders. Recently, we have focused on behavior, nutrition and metabolism in rodent models of social defeat to elucidate how social stresses affect animals. In this review, recent significant progress in studies related to animal social defeat models are described. In the field of animal science, these stress models may contribute to advances in the development of functional foods and in the management of animal welfare. © 2017 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.
Wei, Wei-Zen; Jones, Richard F; Juhasz, Csaba; Gibson, Heather; Veenstra, Jesse
Advances in cancer vaccine development are facilitated by animal models reflecting key features of human cancer and its interface with host immunity. Several series of transplantable preneoplastic and neoplastic mouse mammary lesions have been used to delineate mechanisms of anti-tumor immunity. Mimicking immune tolerance to tumor-associated antigens (TAA) such as HER2/neu, transgenic mice developing spontaneous mammary tumors are strong model systems for pre-clinical vaccine testing. In these models, HER2 DNA vaccines are easily administered, well-tolerated, and induce both humoral and cellular immunity. Although engineered mouse strains have advanced cancer immunotherapy, basic shortcomings remain. For example, multiple mouse strains have to be tested to recapitulate genetic regulation of immune tolerance in humans. Outbred domestic felines more closely parallel humans in the natural development of HER2 positive breast cancer and their varying genetic background. Electrovaccination with heterologous HER2 DNA induces robust adaptive immune responses in cats. Importantly, homologous feline HER2 DNA with a single amino acid substitution elicits unique antibodies to feline mammary tumor cells, unlocking a new vaccine principle. As an alternative approach to targeted vaccination, non-surgical tumor ablation such as cryoablation induces anti-tumor immunity via in situ immunization, particularly when combined with toll-like receptor (TLR) agonist. As strategies for vaccination advance, non-invasive monitoring of host response becomes imperative. As an example, magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning following administration of tryptophan metabolism tracer [11C]-alpha-methyl-tryptophan (AMT) provides non-invasive imaging of both tumor growth and metabolic activities. Because AMT is a substrate of indoleamine-pyrrole 2,3-dioxygenase (IDO), an enzyme that produces the immune regulatory molecule kynurenine, AMT imaging can provide
Wong, R M Y; Choy, M H V; Li, M C M; Leung, K-S; K-H Chow, S; Cheung, W-H; Cheng, J C Y
The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models. A literature search was performed on the Pubmed, Embase, and Web of Science databases, and relevant articles were selected. A total of 19 studies were included. Information on the animal, induction of osteoporosis, fracture technique, site and fixation, healing results, and utility of the model were extracted. Fracture techniques included drill hole defects (3 of 19), bone defects (3 of 19), partial osteotomy (1 of 19), and complete osteotomies (12 of 19). Drill hole models and incomplete osteotomy models are easy to perform and allow the study of therapeutic agents but do not represent the usual clinical setting. Additionally, biomaterials can be filled into drill hole defects for analysis. Complete osteotomy models are most commonly used and are best suited for the investigation of therapeutic drugs or noninvasive interventions. The metaphyseal defect models allow the study of biomaterials, which are associated with complex and comminuted osteoporotic fractures. For a clinically relevant model, we propose that an animal model should satisfy the following criteria to study osteoporotic fracture healing: 1) induction of osteoporosis, 2) complete osteotomy or defect at the metaphysis unilaterally, and 3) internal fixation. Cite this article : R. M. Y. Wong, M. H. V. Choy, M. C. M. Li, K-S. Leung, S. K-H. Chow, W-H. Cheung, J. C. Y. Cheng. A systematic review of current osteoporotic metaphyseal fracture animal models. Bone Joint Res 2018;7:6-11. DOI: 10.1302/2046-3758.71.BJR-2016-0334.R2. © 2018 Wong et al.
Nikolaos P. Daskalakis
Full Text Available The extent to which animal studies can be relevant to military posttraumatic stress disorder (PTSD continues to be a matter of discussion. Some features of the clinical syndrome are more easily modeled than others. In the animal literature, a great deal of attention is focused on modeling the characteristics of military exposures and their impact on measurable behaviors and biological parameters. There are many issues to consider regarding the ecological validity of predator, social defeat or immobilization stress to combat-related experience. In contrast, less attention has been paid to individual variation following these exposures. Such variation is critical to understand how individual differences in the response to military trauma exposure may result to PTSD or resilience. It is important to consider potential differences in biological findings when comparing extremely exposed to non-exposed animals, versus those that result from examining individual differences. Animal models of military PTSD are also critical in advancing efforts in clinical treatment. In an ideal translational approach to study deployment related outcomes, information from humans and animals, blood and brain, should be carefully considered in tandem, possibly even computed simultaneously, to identify molecules, pathways and networks that are likely to be the key drivers of military PTSD symptoms. With the use novel biological methodologies (e.g., optogenetics in the animal models, critical genes and pathways can be tuned up or down (rather than over-expressed or ablated completely in discrete brain regions. Such techniques together with pre-and post-deployment human imaging will accelerate the identification of novel pharmacological and non-pharmacological intervention strategies.
Beth L. Volpov
Full Text Available Dive characteristics and dive shape are often used to infer foraging success in pinnipeds. However, these inferences have not been directly validated in the field with video, and it remains unclear if this method can be applied to benthic foraging animals. This study assessed the ability of dive characteristics from time-depth recorders (TDR to predict attempted prey capture events (APC that were directly observed on animal-borne video in Australian fur seals (Arctocephalus pusillus doriferus, n=11. The most parsimonious model predicting the probability of a dive with ≥1 APC on video included only descent rate as a predictor variable. The majority (94% of the 389 total APC were successful, and the majority of the dives (68% contained at least one successful APC. The best model predicting these successful dives included descent rate as a predictor. Comparisons of the TDR model predictions to video yielded a maximum accuracy of 77.5% in classifying dives as either APC or non-APC or 77.1% in classifying dives as successful verses unsuccessful. Foraging intensity, measured as either total APC per dive or total successful APC per dive, was best predicted by bottom duration and ascent rate. The accuracy in predicting total APC per dive varied based on the number of APC per dive with maximum accuracy occurring at 1 APC for both total (54% and only successful APC (52%. Results from this study linking verified foraging dives to dive characteristics potentially opens the door to decades of historical TDR datasets across several otariid species.
Hoffman, Andrew M; Dow, Steven W
Studies to evaluate the therapeutic potential of stem cells in humans would benefit from more realistic animal models. In veterinary medicine, companion animals naturally develop many diseases that resemble human conditions, therefore, representing a novel source of preclinical models. To understand how companion animal disease models are being studied for this purpose, we reviewed the literature between 2008 and 2015 for reports on stem cell therapies in dogs and cats, excluding laboratory animals, induced disease models, cancer, and case reports. Disease models included osteoarthritis, intervertebral disc degeneration, dilated cardiomyopathy, inflammatory bowel diseases, Crohn's fistulas, meningoencephalomyelitis (multiple sclerosis-like), keratoconjunctivitis sicca (Sjogren's syndrome-like), atopic dermatitis, and chronic (end-stage) kidney disease. Stem cells evaluated in these studies included mesenchymal stem-stromal cells (MSC, 17/19 trials), olfactory ensheathing cells (OEC, 1 trial), or neural lineage cells derived from bone marrow MSC (1 trial), and 16/19 studies were performed in dogs. The MSC studies (13/17) used adipose tissue-derived MSC from either allogeneic (8/13) or autologous (5/13) sources. The majority of studies were open label, uncontrolled studies. Endpoints and protocols were feasible, and the stem cell therapies were reportedly safe and elicited beneficial patient responses in all but two of the trials. In conclusion, companion animals with naturally occurring diseases analogous to human conditions can be recruited into clinical trials and provide realistic insight into feasibility, safety, and biologic activity of novel stem cell therapies. However, improvements in the rigor of manufacturing, study design, and regulatory compliance will be needed to better utilize these models. Stem Cells 2016;34:1709-1729. © 2016 AlphaMed Press.
Full Text Available Due to current improvements in techniques for islet isolation and transplantation and protocols for immunosuppressants, islet transplantation has become an effective treatment for severe diabetes patients. Many diabetic animal models have contributed to such improvements. In this paper, we focus on 3 types of models with different mechanisms for inducing diabetes mellitus (DM: models induced by drugs including streptozotocin (STZ, pancreatomized models, and spontaneous models due to autoimmunity. STZ-induced diabetes is one of the most commonly used experimental diabetic models and is employed using many specimens including rodents, pigs or monkeys. The management of STZ models is well established for islet studies. Pancreatomized models reveal different aspects compared to STZ-induced models in terms of loss of function in the increase and decrease of blood glucose and therefore are useful for evaluating the condition in total pancreatomized patients. Spontaneous models are useful for preclinical studies including the assessment of immunosuppressants because such models involve the same mechanisms as type 1 DM in the clinical setting. In conclusion, islet researchers should select suitable diabetic animal models according to the aim of the study.
Chujitarom, Wannaporn; Piriyasurawong, Pallop
This study aims to synthesize an Animation Augmented Reality Book Model (AAR Book Model) to enhance teamwork and to assess the AAR Book Model to enhance teamwork. Samples are five specialists that consist of one animation specialist, two communication and information technology specialists, and two teaching model design specialists, selected by…
Results indicate that GIS model developed for parasitic diseases based on growing degree day (GDD) concept can be applied to tsetse-transmitted trypanosomosis. GIS for animal trypanosomosis was created using Food and Agriculture Organization – Crop Production System Zones (FAO-CPSZ) database and Normalized ...
Korstanje, Ron; DiPetrillo, K.
Identifying genes underlying common forms of kidney disease in humans has proven difficult, expensive, and time consuming. Quantitative trait loci (QTL) for several complex traits are concordant among mice, rats, and humans, suggesting that genetic findings from these animal models are relevant to
Female Sexual Dysfunction (FSD) is a disorder that affects around 40% of the population. Low sexual arousal and low sexual desire are the most common problems. The mechanisms underlying the disorder are still unclear. The aims of this thesis were 1) the search for animal models of FSD, 2) the
Jena, Ananta Kumar
Adenosine triphosphate (ATP) is the molecular unit of intracellular energy and it is the product of oxidative phosphorylation of cellular respiration uses in cellular processes. The study explores the growth of the misconception levels amongst the learners and evaluates the effectiveness of animation model over traditional methods. The data…
van der Heiden, Kim; Hoogendoorn, Ayla; Daemen, Mat J.; Gijsen, Frank J. H.
Rupture of atherosclerotic plaques is the main cause of acute cardiovascular events. Animal models of plaque rupture are rare but essential for testing new imaging modalities to enable diagnosis of the patient at risk. Moreover, they enable the design of new treatment strategies to prevent plaque
Vodička, Petr; Smetana Jr., K.; Dvořánková, B.; Emerick, T.; Xu, Y.; Ourednik, J.; Ourednik, V.; Motlík, Jan
Roč. 1049, - (2005), s. 161-171 ISSN 0077-8923 R&D Projects: GA MŠk(CZ) LN00A065 Institutional research plan: CEZ:AV0Z50450515 Keywords : animal model * stem cell * transgenic pig Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.971, year: 2005
An animal model utilizes all relationships available in a given data set. Estimates for variance components for additive direct, additive maternal, maternal environmental and direct environmental effects, and their covariances between direct and maternal genetic effects for post weaning growth traits have been obtained with ...
Modeling herbivorous animal digestive system as 3- continuous stirred tank reactor (CSTR) and 1-plug flow reactor (PFR) in series with specific reference to ... This shows the efficiency of each reactor at converting the purely lignocellulosics substrates to useful products like protein, vitamin, fatty acid and the bye-products.
Brouwer, E.; Huitema, M. G.; Klok, P. A.; de Weerd, H.; Tervaert, J. W.; Weening, J. J.; Kallenberg, C. G.
To develop an animal model for antimyeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN), we immunized Brown Norway rats with MPO and localized a neutrophil lysosomal enzyme extract, primarily consisting of MPO and elastinolytic enzymes, plus H2O2, the substrate of MPO,
BROUWER, E; HUITEMA, MG; KLOK, PA; DEWEERD, H; TERVAERT, JWC; WEENING, JJ; KALLENBERG, CGM
To develop an animal model for antimyeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN), we immunized Brown Norway rats with MPO and localized a neutrophil lysosomal enzyme extract, primarily consisting of MPO and elastinolytic enzymes, plus H2O2, the substrate of MPO,
Bem, Reinout A.; Domachowske, Joseph B.; Rosenberg, Helene F.
Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for
Huisman, Floor; van Lienden, Krijn P.; Damude, Samantha; Hoekstra, Lisette T.; van Gulik, Thomas M.
Portal vein embolization (PVE) is a preoperative intervention to increase the future remnant liver (FRL) through regeneration of the non-embolized liver lobes. This review assesses all the relevant animal models of PVE available, to guide researchers who intend to study PVE. We performed a
Kollias, G.; Papadaki, P.; Apparailly, F.; Vervoordeldonk, M.J.; Holmdahl, R.; Baumans, V.; Desaintes, C.; Di Santo, J.; Distler, J.; Garside, P.; Hegen, M.; Huizinga, T.W.J.; Jüngel, A.; Klareskog, L.; McInnes, I.; Ragoussis, I.; Schett, G.; Hart, B.t.; Tak, P.P.; Toes, R.; van den Berg, W.; Wurst, W.; Gay, S.
The development of novel treatments for rheumatoid arthritis (RA) requires the interplay between clinical observations and studies in animal models. Given the complex molecular pathogenesis and highly heterogeneous clinical picture of RA, there is an urgent need to dissect its multifactorial nature
Daetwyler, Hans D.; Calus, Mario P. L.; Pong-Wong, Ricardo; de los Campos, Gustavo; Hickey, John M.
The genomic prediction of phenotypes and breeding values in animals and plants has developed rapidly into its own research field. Results of genomic prediction studies are often difficult to compare because data simulation varies, real or simulated data are not fully described, and not all relevant results are reported. In addition, some new methods have been compared only in limited genetic architectures, leading to potentially misleading conclusions. In this article we review simulation procedures, discuss validation and reporting of results, and apply benchmark procedures for a variety of genomic prediction methods in simulated and real example data. Plant and animal breeding programs are being transformed by the use of genomic data, which are becoming widely available and cost-effective to predict genetic merit. A large number of genomic prediction studies have been published using both simulated and real data. The relative novelty of this area of research has made the development of scientific conventions difficult with regard to description of the real data, simulation of genomes, validation and reporting of results, and forward in time methods. In this review article we discuss the generation of simulated genotype and phenotype data, using approaches such as the coalescent and forward in time simulation. We outline ways to validate simulated data and genomic prediction results, including cross-validation. The accuracy and bias of genomic prediction are highlighted as performance indicators that should be reported. We suggest that a measure of relatedness between the reference and validation individuals be reported, as its impact on the accuracy of genomic prediction is substantial. A large number of methods were compared in example simulated and real (pine and wheat) data sets, all of which are publicly available. In our limited simulations, most methods performed similarly in traits with a large number of quantitative trait loci (QTL), whereas in traits
... the Animal Rule; Notice of Public Meeting; and Reopening of Comment Period AGENCY: Food and Drug... challenges as addressed in the draft document entitled ``Guidance for ] Industry: Animal Models--Essential Elements to Address Efficacy Under the Animal Rule'' dated January 2009 (Draft Guidance), and as related to...
Risselada, Hans; Verhoef, Peter C.; Bijmolt, Tammo H. A.
In this paper, we study the staying power of various churn prediction models. Staying power is defined as the predictive performance of a model in a number of periods after the estimation period. We examine two methods, logit models and classification trees, both with and without applying a bagging
Burcharth, J; Pommergaard, H-C; Klein, M
Background: Incisional hernia (IH) is a well-known complication after abdominal surgical procedures. The exact etiology of IH is still unknown even though many risk factors have been suggested. The aim of this study was to create an animal model of a weakly healed abdominal fascia that could...... be used to evaluate the actively healing fascia. Such an animal model may promote future research in the prevention of IH. Methods: 86 male Sprague-Dawley rats were used to establish a model involving six experiments (experiments A-F). Mechanical testing of the breaking strength of the healed fascia...... was performed by testing tissue strips from the healed fascia versus the unincised control fascia 7 and 28 days postoperatively. Results: During the six experiments a healing model was created that produced significantly weaker coherent fascia when compared with the control tissue measured in terms...
Hagstrom, Danielle; Cochet-Escartin, Olivier; Zhang, Siqi; Khuu, Cindy; Collins, Eva-Maria S
Traditional toxicology testing has relied on low-throughput, expensive mammalian studies; however, timely testing of the large number of environmental toxicants requires new in vitro and in vivo platforms for inexpensive medium- to high-throughput screening. Herein, we describe the suitability of the asexual freshwater planarian Dugesia japonica as a new animal model for the study of developmental neurotoxicology. As these asexual animals reproduce by binary fission, followed by regeneration of missing body structures within approximately 1 week, development and regeneration occur through similar processes allowing us to induce neurodevelopment "at will" through amputation. This short time scale and the comparable sizes of full and regenerating animals enable parallel experiments in adults and developing worms to determine development-specific aspects of toxicity. Because the planarian brain, despite its simplicity, is structurally and molecularly similar to the mammalian brain, we are able to ascertain neurodevelopmental toxicity that is relevant to humans. As a proof of concept, we developed a 5-step semiautomatic screening platform to characterize the toxicity of 9 known neurotoxicants (consisting of common solvents, pesticides, and detergents) and a neutral agent, glucose, and quantified effects on viability, stimulated and unstimulated behavior, regeneration, and brain structure. Comparisons of our findings with other alternative toxicology animal models, such as zebrafish larvae and nematodes, demonstrated that planarians are comparably sensitive to the tested chemicals. In addition, we found that certain compounds induced adverse effects specifically in developing animals. We thus conclude that planarians offer new complementary opportunities for developmental neurotoxicology animal models. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: email@example.com.
Noda, Kousuke; Melhorn, Mark I.; Zandi, Souska; Frimmel, Sonja; Tayyari, Faryan; Hisatomi, Toshio; Almulki, Lama; Pronczuk, Andrzej; Hayes, K. C.; Hafezi-Moghadam, Ali
Metabolic syndrome (MetS) is a prevalent and complex disease, characterized by the variable coexistence of obesity, dyslipidemia, hyperinsulinaemia, and hypertension. The alarming rise in the prevalence of metabolic disorders makes it imperative to innovate preventive or therapeutic measures for MetS and its complications. However, the elucidation of the pathogenesis of MetS has been hampered by the lack of realistic models. For example, the existing animal models of MetS, i.e., genetically e...
Oldham, J.D.; Eayres, H.; Emmans, G.C.; Hou, X.Z.; Illius, A.W.; Jessop, N.S.; Matthewman, R.W.
A general model is presented of the relationships between animal and food characteristics which help lead to predictions of food consumption and animal performance. It is an important part of this scheme that equal weight is given to the description of food and animal characteristics. The results of some experiments are given suggesting that ruminants can select between feeds to meet their nutrient needs and that, in growing animals, the physical capacity to bite is an important determinant of grazing efficiency and ecology. Studies with growing lambs of the energetic efficiency of growth suggest that variation in the energy cost of protein accretion may be a more important determinant of overall energetic efficiency of growth than is conventionally supposed. In lactating animals that also exercise, milk protein and lactose yields fall during exercise and this effect is difficult to counteract by protein and/or starch supplementation of straw diets. Studies of forage substitution by supplements have not revealed differences in substitution rate with age in sheep. (author). 22 refs, 6 figs, 2 tabs
Experimental animal model worked out in Muenchen is discussed in which late postradiation reaction in Wistar rats following local irradiation of the colon manifests itself by appearance of colonic stenoses causing death of the animal. Clinical symptoms of this reaction together with results of histopathologic examination of the excised parts of the colon localized in the irradiated area are discussed. The relationships effect-dose obtained in this system for X radiation applying different regimen of dose fractionation and different total times of irradiation are presented. 8 refs., 5 figs., 1 tab. (author)
Andrade, Ana Laura Martins de; Parisi, Julia Risso; Brassolatti, Patrícia; Parizotto, Nivaldo Antonio
Abstract Purpose: To present an alternative experimental model of third degree burn of easy reproducibility. Methods: Eighteen male Wister rats were randomly divided into three groups, 6 of which were allocated to each group. A soldering iron coupled to an aluminum plate was used to produce burn, at a temperature of 150ºC, with different exposure times per group. Group 5 (G5) animals were burned at 150°C with exposure time of 5 seconds; Group 10 (G10) the animals were burned at 150°C with e...
Slater, Leo B
Through the examination of avian malarias as models of infectious human disease, this paper reveals the kinds of claims that scientists and physicians made on the basis of animal models-biological systems in the laboratory and the field-and what characteristics made for congruence between these models and human malaria. The focus is on the period between 1895 and 1945, and on the genesis and trajectory of certain animal models of malaria within specific locations, such as the Johns Hopkins School of Hygiene and Public Health in Baltimore and Bayer (I. G. Farben) in Elberfeld. These exemplars illustrate a diversity of approaches to malaria-as-disease, and the difficulties of framing aspects of this disease complex within an animal or laboratory system. The diversity and nearness to wild types of the birds, protozoan parasites, and mosquitoes that made up these malaria models contributed a great deal to the complexity of the models. Avian malarias, adopted with enthusiasm, were essential to the success of the U.S. antimalarial program during World War II.
Human enterovirus 71 (EV71) has emerged as a neuroinvasive virus that is responsible for several outbreaks in the Asia-Pacific region over the past 15 years. Appropriate animal models are needed to understand EV71 neuropathogenesis better and to facilitate the development of effective vaccines and drugs. Non-human primate models have been used to characterize and evaluate the neurovirulence of EV71 after the early outbreaks in late 1990s. However, these models were not suitable for assessing the neurovirulence level of the virus and were associated with ethical and economic difficulties in terms of broad application. Several strategies have been applied to develop mouse models of EV71 infection, including strategies that employ virus adaption and immunodeficient hosts. Although these mouse models do not closely mimic human disease, they have been applied to determine the pathogenesis of and treatment and prevention of the disease. EV71 receptor-transgenic mouse models have recently been developed and have significantly advanced our understanding of the biological features of the virus and the host-parasite interactions. Overall, each of these models has advantages and disadvantages, and these models are differentially suited for studies of EV71 pathogenesis and/or the pre-clinical testing of antiviral drugs and vaccines. In this paper, we review the characteristics, applications and limitation of these EV71 animal models, including non-human primate and mouse models. PMID:24742252
Nakayama, Eri; Saijo, Masayuki
Ebola and Marburg hemorrhagic fevers (EHF and MHF) are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus), respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4) pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using non-human primates (NHPs) and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics. PMID:24046765
Full Text Available Ebola and Marburg hemorrhagic fevers (EHF and MHF are caused by the Filoviridae family, Ebolavirus and Marburgvirus (ebolavirus and marburgvirus, respectively. These severe diseases have high mortality rates in humans. Although EHF and MHF are endemic to sub-Saharan Africa. A novel filovirus, Lloviu virus, which is genetically distinct from ebolavirus and marburgvirus, was recently discovered in Spain where filoviral hemorrhagic fever had never been reported. The virulence of this virus has not been determined. Ebolavirus and marburgvirus are classified as biosafety level-4 (BSL-4 pathogens and Category A agents, for which the US government requires preparedness in case of bioterrorism. Therefore, preventive measures against these viral hemorrhagic fevers should be prepared, not only in disease-endemic regions, but also in disease-free countries. Diagnostics, vaccines, and therapeutics need to be developed, and therefore the establishment of animal models for EHF and MHF is invaluable. Several animal models have been developed for EHF and MHF using nonhuman primates (NHPs and rodents, which are crucial to understand pathophysiology and to develop diagnostics, vaccines, and therapeutics. Rhesus and cynomolgus macaques are representative models of filovirus infection as they exhibit remarkably similar symptoms to those observed in humans. However, the NHP models have practical and ethical problems that limit their experimental use. Furthermore, there are no inbred and genetically manipulated strains of NHP. Rodent models such as mouse, guinea pig, and hamster, have also been developed. However, these rodent models require adaptation of the virus to produce lethal disease and do not mirror all symptoms of human filovirus infection. This review article provides an outline of the clinical features of EHF and MHF in animals, including humans, and discusses how the animal models have been developed to study pathophysiology, vaccines, and therapeutics.
Muñoz-Tamayo, R; Puillet, L; Daniel, J B; Sauvant, D; Martin, O; Taghipoor, M; Blavy, P
What is a good (useful) mathematical model in animal science? For models constructed for prediction purposes, the question of model adequacy (usefulness) has been traditionally tackled by statistical analysis applied to observed experimental data relative to model-predicted variables. However, little attention has been paid to analytic tools that exploit the mathematical properties of the model equations. For example, in the context of model calibration, before attempting a numerical estimation of the model parameters, we might want to know if we have any chance of success in estimating a unique best value of the model parameters from available measurements. This question of uniqueness is referred to as structural identifiability; a mathematical property that is defined on the sole basis of the model structure within a hypothetical ideal experiment determined by a setting of model inputs (stimuli) and observable variables (measurements). Structural identifiability analysis applied to dynamic models described by ordinary differential equations (ODEs) is a common practice in control engineering and system identification. This analysis demands mathematical technicalities that are beyond the academic background of animal science, which might explain the lack of pervasiveness of identifiability analysis in animal science modelling. To fill this gap, in this paper we address the analysis of structural identifiability from a practitioner perspective by capitalizing on the use of dedicated software tools. Our objectives are (i) to provide a comprehensive explanation of the structural identifiability notion for the community of animal science modelling, (ii) to assess the relevance of identifiability analysis in animal science modelling and (iii) to motivate the community to use identifiability analysis in the modelling practice (when the identifiability question is relevant). We focus our study on ODE models. By using illustrative examples that include published
Jørgensen, John Bagterp; Jørgensen, Sten Bay
Single and multi-step prediction-error-methods based on the maximum likelihood and least squares criteria are compared. The prediction-error methods studied are based on predictions using the Kalman filter and Kalman predictors for a linear discrete-time stochastic state space model, which is a r...
Full Text Available Autoimmune nephritis triggered by metallic ions was assessed in a Long-Evans rat model. The parameters evaluated included antinuclear autoantibody production, kidney damage mediated by immune complexes detected by immunofluorescence, and renal function tested by retention of nitrogen waste products and proteinuria. To accomplish our goal, the animals were treated with the following ionic metals: HgCl2, CuSO4, AgNO3, and Pb(NO32. A group without ionic metals was used as the control. The results of the present investigation demonstrated that metallic ions triggered antinuclear antibody production in 60% of animals, some of them with anti-DNA specificity. Furthermore, all animals treated with heavy metals developed toxic glomerulonephritis with immune complex deposition along the mesangium and membranes. These phenomena were accompanied by proteinuria and increased concentrations of urea. Based on these results, we conclude that metallic ions may induce experimental autoimmune nephritis.
Cellini, L; Marzio, L; Ferrero, G; Del Vino, A; Di Campli, E; Grossi, L; Toracchio, S; Artese, L
An experimental murine model was studied to evaluate the orogastrointestinal colonization of Helicobacter pylori and the animal-to-animal transmission. Balb/C mice were infected with H. pylori and housed with uninoculated mice in cages with and without a grate on the floor. Mice were killed after 7, 14, 30, and 45 days, and samples from the esophagus, stomach, small intestine, colon, and rectum were analyzed for H. pylori by PCR and immunohistochemistry and for histological changes. Bacterial colonization was assessed also by culture from stomach samples. H. pylori was cultured by stomach samples of infected mice at 7, 14, and 30 days. Using PCR and immunohistochemistry, H. pylori was detected in inoculated and uninoculated mice in all areas examined, with an high percentage of positive samples in the esophagus and stomach. Moreover transmission was detected, without differences, regardless of whether mice were housed with or without a grate on the floor, supporting an orooral animal transmission.
Full Text Available Tanya A Enderli, Stephanie R Burtch, Jara N Templet, Alessandra Carriero Department of Biomedical Engineering, Florida Institute of Technology, Melbourne, FL, USA Abstract: Osteogenesis imperfecta (OI, commonly known as brittle bone disease, is a genetic disease characterized by extreme bone fragility and consequent skeletal deformities. This connective tissue disorder is caused by mutations in the quality and quantity of the collagen that in turn affect the overall mechanical integrity of the bone, increasing its vulnerability to fracture. Animal models of the disease have played a critical role in the understanding of the pathology and causes of OI and in the investigation of a broad range of clinical therapies for the disease. Currently, at least 20 animal models have been officially recognized to represent the phenotype and biochemistry of the 17 different types of OI in humans. These include mice, dogs, and fish. Here, we describe each of the animal models and the type of OI they represent, and present their application in clinical research for treatments of OI, such as drug therapies (ie, bisphosphonates and sclerostin and mechanical (ie, vibrational loading. In the future, different dosages and lengths of treatment need to be further investigated on different animal models of OI using potentially promising treatments, such as cellular and chaperone therapies. A combination of therapies may also offer a viable treatment regime to improve bone quality and reduce fragility in animals before being introduced into clinical trials for OI patients. Keywords: OI, brittle bone, clinical research, mouse, dog, zebrafish
Lowell, Jennifer L; Eisen, Rebecca J; Schotthoefer, Anna M; Xiaocheng, Liang; Montenieri, John A; Tanda, Dale; Pape, John; Schriefer, Martin E; Antolin, Michael F; Gage, Kenneth L
Human plague risks (Yersinia pestis infection) are greatest when epizootics cause high mortality among this bacterium's natural rodent hosts. Therefore, health departments in plague-endemic areas commonly establish animal-based surveillance programs to monitor Y. pestis infection among plague hosts and vectors. The primary objectives of our study were to determine whether passive animal-based plague surveillance samples collected in Colorado from 1991 to 2005 were sampled from high human plague risk areas and whether these samples provided information useful for predicting human plague case locations. By comparing locations of plague-positive animal samples with a previously constructed GIS-based plague risk model, we determined that the majority of plague-positive Gunnison's prairie dogs (100%) and non-prairie dog sciurids (85.82%), and moderately high percentages of sigmodontine rodents (71.4%), domestic cats (69.3%), coyotes (62.9%), and domestic dogs (62.5%) were recovered within 1 km of the nearest area posing high peridomestic risk to humans. In contrast, the majority of white-tailed prairie dog (66.7%), leporid (cottontailed and jack rabbits) (71.4%), and black-tailed prairie dog (93.0%) samples originated more than 1 km from the nearest human risk habitat. Plague-positive animals or their fleas were rarely (one of 19 cases) collected within 2 km of a case exposure site during the 24 months preceding the dates of illness onset for these cases. Low spatial accuracy for identifying epizootic activity prior to human plague cases suggested that other mammalian species or their fleas are likely more important sources of human infection in high plague risk areas. To address this issue, epidemiological observations and multi-locus variable number tandem repeat analyses (MLVA) were used to preliminarily identify chipmunks as an under-sampled, but potentially important, species for human plague risk in Colorado.
Hickey, John M; Chiurugwi, Tinashe; Mackay, Ian; Powell, Wayne
The rate of annual yield increases for major staple crops must more than double relative to current levels in order to feed a predicted global population of 9 billion by 2050. Controlled hybridization and selective breeding have been used for centuries to adapt plant and animal species for human use. However, achieving higher, sustainable rates of improvement in yields in various species will require renewed genetic interventions and dramatic improvement of agricultural practices. Genomic prediction of breeding values has the potential to improve selection, reduce costs and provide a platform that unifies breeding approaches, biological discovery, and tools and methods. Here we compare and contrast some animal and plant breeding approaches to make a case for bringing the two together through the application of genomic selection. We propose a strategy for the use of genomic selection as a unifying approach to deliver innovative 'step changes' in the rate of genetic gain at scale.
Jackson, Mark P; Rahman, Asif; Lafon, Belen; Kronberg, Gregory; Ling, Doris; Parra, Lucas C; Bikson, Marom
The objective of this review is to summarize the contribution of animal research using direct current stimulation (DCS) to our understanding of the physiological effects of transcranial direct current stimulation (tDCS). We comprehensively address experimental methodology in animal studies, broadly classified as: (1) transcranial stimulation; (2) direct cortical stimulation in vivo and (3) in vitro models. In each case advantages and disadvantages for translational research are discussed including dose translation and the overarching "quasi-uniform" assumption, which underpins translational relevance in all animal models of tDCS. Terminology such as anode, cathode, inward current, outward current, current density, electric field, and uniform are defined. Though we put key animal experiments spanning decades in perspective, our goal is not simply an exhaustive cataloging of relevant animal studies, but rather to put them in context of ongoing efforts to improve tDCS. Cellular targets, including excitatory neuronal somas, dendrites, axons, interneurons, glial cells, and endothelial cells are considered. We emphasize neurons are always depolarized and hyperpolarized such that effects of DCS on neuronal excitability can only be evaluated within subcellular regions of the neuron. Findings from animal studies on the effects of DCS on plasticity (LTP/LTD) and network oscillations are reviewed extensively. Any endogenous phenomena dependent on membrane potential changes are, in theory, susceptible to modulation by DCS. The relevance of morphological changes (galvanotropy) to tDCS is also considered, as we suggest microscopic migration of axon terminals or dendritic spines may be relevant during tDCS. A majority of clinical studies using tDCS employ a simplistic dose strategy where excitability is singularly increased or decreased under the anode and cathode, respectively. We discuss how this strategy, itself based on classic animal studies, cannot account for the
Roth, J A; Flaming, K P
Development of immunomodulators for use in food producing animals is an active area of research. This research has generally incorporated aspects of immunosuppression in model systems. This methodology is appropriate because most of the research has been aimed at developing immunomodulators for certain economically significant diseases in which immunosuppression is believed to be an important component of their pathogenesis. The primary focus has been on stress-associated diseases (especially bovine respiratory disease), infectious diseases in young animals, and mastitis. The model systems used have limitations, but they have demonstrated that immunomodulators are capable of significantly increasing resistance to these important infectious disease syndromes. As our understanding of molecular immunology increases and as more potential immunomodulators become available, the use of relevant model systems should greatly aid advancement in the field of immunomodulation.
Stafstrom, Carl E
Infantile spasms is a developmental epilepsy syndrome with unique clinical and EEG features, a specific pattern of pharmacological responsiveness, and poor outcome in terms of cognition and epilepsy. Despite the devastating nature of infantile spasms, little is known about its pathogenesis. Until recently, there has been no animal model available to investigate the pathophysiology of the syndrome or to generate and test novel therapies. Now, several promising animal models have emerged, spanning the etiological spectrum from genetic causes (e.g., Down syndrome or Aristaless-related homeobox [ARX] mutation) to acquired causes (e.g., endogenous and exogenous toxins or stress hormones with convulsant activity or blockade of neural activity). These new models are discussed in this review, with emphasis on the insights each can provide for understanding, treating, and preventing infantile spasms. PMID:19471616
Full Text Available Objective To reproduce an animal model of landmine blast injuries for studying its mechanism and characteristics. Methods Fifteen healthy New Zealand white rabbits (body weight 1.9-2.4 kg were prepared as experimental animals. Punctiform burster was used to simulate the landmine, and it was electrically detonated far away to produce landmine blast injuries on unilateral hind limb of rabbits in upright state. The vital signs before and 5min, 15min, 30min, 45min, 1h, 2h, 3h, 6h, 9h and 12h after injuries were recorded. Autopsy of dead animals was performed immediately and the survivors were sacrificed for pathological examination 6h and 12h after the injury. Macroscopic and microscopic changes in the injured limb and distant organs were observed. Fifteen random adult body weights were generated by random number table, and the explosive energy of M14 landmine (about 29g TNT explosive energy was simulated, to compare the ratio of explosive force equivalent to weight calculated between experimental animals and randomly selected adults. Results No significant change in blood pressure was observed at different time points before and after injuries. A broom-like change was found in the injured limb by the general observation. The subareas and pathological changes of injured limb coincided with the typical limb injuries produced by landmine explosion. Damage in different degrees was found in distant organs, and the wound characteristics and injury of major organs were in accordance with the reports of relevant literature. The ratio of explosive equivalent to weight of experimental animals (0.50±0.04g TNT/kg was similar to that of randomly selected adults (0.51±0.05g TNT/kg. Conclusion The present animal model could simulate the landmine explosive injuries, and may be used in research of landmine explosive injuries. DOI: 10.11855/j.issn.0577-7402.2014.01.14
Noda, Kousuke; Melhorn, Mark I; Zandi, Souska; Frimmel, Sonja; Tayyari, Faryan; Hisatomi, Toshio; Almulki, Lama; Pronczuk, Andrzej; Hayes, K C; Hafezi-Moghadam, Ali
Metabolic syndrome (MetS) is a prevalent and complex disease, characterized by the variable coexistence of obesity, dyslipidemia, hyperinsulinaemia, and hypertension. The alarming rise in the prevalence of metabolic disorders makes it imperative to innovate preventive or therapeutic measures for MetS and its complications. However, the elucidation of the pathogenesis of MetS has been hampered by the lack of realistic models. For example, the existing animal models of MetS, i.e., genetically engineered rodents, imitate certain aspects of the disease, while lacking other important components. Defining the natural course of MetS in a spontaneous animal model of the disease would be desirable. Here, we introduce the Nile grass rat (NGR), Arvicanthis niloticus, as a novel model of MetS. Studies of over 1100 NGRs in captivity, fed normal chow, revealed that most of these animals spontaneously develop dyslipidemia (P<0.01), and hyperglycemia (P<0.01) by 1 yr of age. Further characterization showed that the diabetic rats develop liver steatosis, abdominal fat accumulation, nephropathy, atrophy of pancreatic islets of Langerhans, fatty streaks in the aorta, and hypertension (P<0.01). Diabetic NGRs in the early phase of the disease develop hyperinsulinemia, and show a strong inverse correlation between plasma adiponectin and HbA1c levels (P<0.01). These data indicate that the NGR is a valuable, spontaneous model for exploring the etiology and pathophysiology of MetS as well as its various complications.
Hickey, John M; Chiurugwi, Tinashe; Mackay, Ian; Powell, Wayne; Implementing Genomic Selection in CGIAR Breeding Programs Workshop Participants
The rate of annual yield increases for major staple crops must more than double relative to current levels in order to feed a predicted global population of 9 billion by 2050. Controlled hybridization and selective breeding have been used for centuries to adapt plant and animal species for human use. However, achieving higher, sustainable rates of improvement in yields in various species will require renewed genetic interventions and dramatic improvement of agricultural practices. Genomic pre...
Birder, Lori; Andersson, Karl-Erik
The etiology of interstitial cystitis/bladder pain syndrome (IC/BPS) remains elusive and may involve multiple causes. To better understand its pathophysiology, many efforts have been made to create IC/BPS models. Most existing models of IC/BPS strive to recreate bladder-related features by applying noxious intravesical or systemic stimuli to healthy animals. These models are useful to help understand various mechanisms; however, they are limited to demonstrating how the bladder and nervous system respond to noxious stimuli, and are not representative of the complex interactions and pathophysiology of IC/BPS. To study the various factors that may be relevant for IC/BPS, at least 3 different types of animal models are commonly used: (1) bladder-centric models, (2) models with complex mechanisms, and (3) psychological and physical stressors/natural disease models. It is obvious that all aspects of the human disease cannot be mimicked by a single model. It may be the case that several models, each contributing to a piece of the puzzle, are required to recreate a reasonable picture of the pathophysiology and time course of the disease(s) diagnosed as IC/BPS, and thus to identify reasonable targets for treatment.
Mavanji, Vijayakumar; Billington, Charles J.; Kotz, Catherine M.; Teske, Jennifer A.
The rapid rise in obesity prevalence in the modern world parallels a significant reduction in restorative sleep (Agras et al., 2004; Dixon et al., 2007; Dixon et al., 2001; Gangwisch and Heymsfield, 2004; Gupta et al., 2002; Sekine et al., 2002; Vioque et al., 2000; Wolk et al., 2003). Reduced sleep time and quality increases the risk for obesity, but the underlying mechanisms remain unclear (Gangwisch et al., 2005; Hicks et al., 1986; Imaki et al., 2002; Jennings et al., 2007; Moreno et al., 2006). A majority of the theories linking human sleep disturbances and obesity rely on self-reported sleep. However, studies with objective measurements of sleep/wake parameters suggest a U-shaped relationship between sleep and obesity. Studies in animal models are needed to improve our understanding of the association between sleep disturbances and obesity. Genetic and experimenter-induced models mimicking characteristics of human obesity are now available and these animal models will be useful in understanding whether sleep disturbances determine propensity for obesity, or result from obesity. These models exhibit weight gain profiles consistently different from control animals. Thus a careful evaluation of animal models will provide insight into the relationship between sleep disturbances and obesity in humans. In this review we first briefly consider the fundamentals of sleep and key sleep disturbances, such as sleep fragmentation and excessive daytime sleepiness (EDS), observed in obese individuals. Then we consider sleep deprivation studies and the role of circadian alterations in obesity. We describe sleep/wake changes in various rodent models of obesity and obesity resistance. Finally, we discuss possible mechanisms linking sleep disturbances with obesity. PMID:22266350
Burrows, Emma L; Hannan, Anthony J
Schizophrenia is a devastating brain disorder caused by a complex and heterogeneous combination of genetic and environmental factors. In order to develop effective new strategies to prevent and treat schizophrenia, valid animal models are required which accurately model the disorder, and ideally provide construct, face and predictive validity. The cognitive deficits in schizophrenia represent some of the most debilitating symptoms and are also currently the most poorly treated. Therefore it is crucial that animal models are able to capture the cognitive dysfunction that characterizes schizophrenia, as well as the negative and psychotic symptoms. The genomes of mice have, prior to the recent gene-editing revolution, proven the most easily manipulable of mammalian laboratory species, and hence most genetic targeting has been performed using mouse models. Importantly, when key environmental factors of relevance to schizophrenia are experimentally manipulated, dramatic changes in the phenotypes of these animal models are often observed. We will review recent studies in rodent models which provide insight into gene-environment interactions in schizophrenia. We will focus specifically on environmental factors which modulate levels of experience-dependent plasticity, including environmental enrichment, cognitive stimulation, physical activity and stress. The insights provided by this research will not only help refine the establishment of optimally valid animal models which facilitate development of novel therapeutics, but will also provide insight into the pathogenesis of schizophrenia, thus identifying molecular and cellular targets for future preclinical and clinical investigations. Copyright © 2015 Elsevier B.V. All rights reserved.
Improve the accuracy of TxDOTs existing pavement performance prediction models through calibrating these models using actual field data obtained from the Pavement Management Information System (PMIS). : Ensure logical performance superiority patte...
Czado, Claudia; Gneiting, Tilmann; Held, Leonhard
.... In case studies, we critique count regression models for patent data, and assess the predictive performance of Bayesian age-period-cohort models for larynx cancer counts in Germany. Key words: Calibration...
Juhl, Rune; Møller, Jan Kloppenborg; Jørgensen, John Bagterp
deterministic and can predict the future perfectly. A more realistic approach would be to allow for randomness in the model due to e.g., the model be too simple or errors in input. We describe a modeling and prediction setup which better reflects reality and suggests stochastic differential equations (SDEs......) for modeling and forecasting. It is argued that this gives models and predictions which better reflect reality. The SDE approach also offers a more adequate framework for modeling and a number of efficient tools for model building. A software package (CTSM-R) for SDE-based modeling is briefly described....... that describes the variation between subjects. The ODE setup implies that the variation for a single subject is described by a single parameter (or vector), namely the variance (covariance) of the residuals. Furthermore the prediction of the states is given as the solution to the ODEs and hence assumed...
Becker, Jill B.
The purpose of this review is to discuss ways to think about and study sex differences in preclinical animal models. We use the framework of addiction, in which animal models have excellent face and construct validity, to illustrate the importance of considering sex differences. There are four types of sex differences: qualitative, quantitative, population, and mechanistic. A better understanding of the ways males and females can differ will help scientists design experiments to characterize better the presence or absence of sex differences in new phenomena that they are investigating. We have outlined major quantitative, population, and mechanistic sex differences in the addiction domain using a heuristic framework of the three established stages of the addiction cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Female rats, in general, acquire the self-administration of drugs and alcohol more rapidly, escalate their drug taking with extended access more rapidly, show more motivational withdrawal, and (where tested in animal models of “craving”) show greater reinstatement. The one exception is that female rats show less motivational withdrawal to alcohol. The bases for these quantitative sex differences appear to be both organizational, in that estradiol-treated neonatal animals show the male phenotype, and activational, in that the female phenotype depends on the effects of gonadal hormones. In animals, differences within the estrous cycle can be observed but are relatively minor. Such hormonal effects seem to be most prevalent during the acquisition of drug taking and less influential once compulsive drug taking is established and are linked largely to progesterone and estradiol. This review emphasizes not only significant differences in the phenotypes of females and males in the domain of addiction but emphasizes the paucity of data to date in our understanding of those differences. PMID:26772794
Horowitz, J. M.
The present review evaluates several assumptions common to a variety of current models for thermoregulation in cold-stressed animals. Three areas covered by the models are discussed: signals to and from the central nervous system (CNS), portions of the CNS involved, and the arrangement of neurons within networks. Assumptions in each of these categories are considered. The evaluation of the models is based on the experimental foundations of the assumptions. Regions of the nervous system concerned here include the hypothalamus, the skin, the spinal cord, the hippocampus, and the septal area of the brain.
Peter A. Horn
Full Text Available Foamy virus (FV vectors have shown great promise for hematopoietic stem cell (HSC gene therapy. Their ability to efficiently deliver transgenes to multi-lineage long-term repopulating cells in large animal models suggests they will be effective for several human hematopoietic diseases. Here, we review FV vector studies in large animal models, including the use of FV vectors with the mutant O6-methylguanine-DNA methyltransferase, MGMTP140K to increase the number of genetically modified cells after transplantation. In these studies, FV vectors have mediated efficient gene transfer to polyclonal repopulating cells using short ex vivo transduction protocols designed to minimize the negative effects of ex vivo culture on stem cell engraftment. In this regard, FV vectors appear superior to gammaretroviral vectors, which require longer ex vivo culture to effect efficient transduction. FV vectors have also compared favorably with lentiviral vectors when directly compared in the dog model. FV vectors have corrected leukocyte adhesion deficiency and pyruvate kinase deficiency in the dog large animal model. FV vectors also appear safer than gammaretroviral vectors based on a reduced frequency of integrants near promoters and also near proto-oncogenes in canine repopulating cells. Together, these studies suggest that FV vectors should be highly effective for several human hematopoietic diseases, including those that will require relatively high percentages of gene-modified cells to achieve clinical benefit.
Full Text Available Apart from teratogenic and pathological effects of zinc deficiency such as the occurrence of skin lesions, anorexia, growth retardation, depressed wound healing, altered immune function, impaired night vision, and alterations in taste and smell acuity, characteristic behavioral changes in animal models and human patients suffering from zinc deficiency have been observed. Given that it is estimated that about 17% of the worldwide population are at risk for zinc deficiency and that zinc deficiency is associated with a variety of brain disorders and disease states in humans, it is of major interest to investigate, how these behavioral changes will affect the individual and a putative course of a disease. Thus, here, we provide a state of the art overview about the behavioral phenotypes observed in various models of zinc deficiency, among them environmentally produced zinc deficient animals as well as animal models based on a genetic alteration of a particular zinc homeostasis gene. Finally, we compare the behavioral phenotypes to the human condition of mild to severe zinc deficiency and provide a model, how zinc deficiency that is associated with many neurodegenerative and neuropsychological disorders might modify the disease pathologies.
Al Shakarchi, Julien; McGrogan, Damian; Van der Veer, Sabine; Sperrin, Matthew; Inston, Nicholas
Haemodialysis (HD) is a lifeline therapy for patients with end-stage renal disease (ESRD). A critical factor in the survival of renal dialysis patients is the surgical creation of vascular access, and international guidelines recommend arteriovenous fistulas (AVF) as the gold standard of vascular access for haemodialysis. Despite this, AVFs have been associated with high failure rates. Although risk factors for AVF failure have been identified, their utility for predicting AVF failure through predictive models remains unclear. The objectives of this review are to systematically and critically assess the methodology and reporting of studies developing prognostic predictive models for AVF outcomes and assess them for suitability in clinical practice. Electronic databases were searched for studies reporting prognostic predictive models for AVF outcomes. Dual review was conducted to identify studies that reported on the development or validation of a model constructed to predict AVF outcome following creation. Data were extracted on study characteristics, risk predictors, statistical methodology, model type, as well as validation process. We included four different studies reporting five different predictive models. Parameters identified that were common to all scoring system were age and cardiovascular disease. This review has found a small number of predictive models in vascular access. The disparity between each study limits the development of a unified predictive model.
Model Predictive Control (MPC) has developed considerably over the last two decades, both within the research control community and in industries. MPC strategy involves the optimization of a performance index with respect to some future control sequence, using predictions of the output signal based on a process model, ...
Rawlings, James B.; Bonné, Dennis; Jørgensen, John Bagterp
In this work, a new model predictive controller is developed that handles unreachable setpoints better than traditional model predictive control methods. The new controller induces an interesting fast/slow asymmetry in the tracking response of the system. Nominal asymptotic stability of the optim...
Wessler, Benjamin S; Lai Yh, Lana; Kramer, Whitney; Cangelosi, Michael; Raman, Gowri; Lutz, Jennifer S; Kent, David M
Clinical prediction models (CPMs) estimate the probability of clinical outcomes and hold the potential to improve decision making and individualize care. For patients with cardiovascular disease, there are numerous CPMs available although the extent of this literature is not well described. We conducted a systematic review for articles containing CPMs for cardiovascular disease published between January 1990 and May 2012. Cardiovascular disease includes coronary heart disease, heart failure, arrhythmias, stroke, venous thromboembolism, and peripheral vascular disease. We created a novel database and characterized CPMs based on the stage of development, population under study, performance, covariates, and predicted outcomes. There are 796 models included in this database. The number of CPMs published each year is increasing steadily over time. Seven hundred seventeen (90%) are de novo CPMs, 21 (3%) are CPM recalibrations, and 58 (7%) are CPM adaptations. This database contains CPMs for 31 index conditions, including 215 CPMs for patients with coronary artery disease, 168 CPMs for population samples, and 79 models for patients with heart failure. There are 77 distinct index/outcome pairings. Of the de novo models in this database, 450 (63%) report a c-statistic and 259 (36%) report some information on calibration. There is an abundance of CPMs available for a wide assortment of cardiovascular disease conditions, with substantial redundancy in the literature. The comparative performance of these models, the consistency of effects and risk estimates across models and the actual and potential clinical impact of this body of literature is poorly understood. © 2015 American Heart Association, Inc.
Letícia Thaís Chendynski; Universidade Estadual de Londrina; Karina G. Angilelli; Universidade Estadual de Londrina; Bruna A. D. Ferreira; Unversidade Esadual de Londrina; Dionisio Borsato; Universidade Estadual de Londrina
The high availability and low cost of animal fat have promoted industrial interest as a partial substitute for soybean oil for transesterification reaction product of synthesis, to reduce costs and maximize profits. This study aimed to apply experimental design for biodiesel production from a mixture of soybean oil, poultry fat, beef tallow and pork lard in order to obtain predictive equations to model the transesterification reaction yield, cloud point, pour point and oxidative stability, wi...
Hutchinson, John M C; Waser, Peter M
Biologists have repeatedly rediscovered classical models from physics predicting collision rates in an ideal gas. These models, and their two-dimensional analogues, have been used to predict rates and durations of encounters among animals or social groups that move randomly and independently, given population density, velocity, and distance at which an encounter occurs. They have helped to separate cases of mixed-species association based on behavioural attraction from those that simply reflect high population densities, and to detect cases of attraction or avoidance among conspecifics. They have been used to estimate the impact of population density, speeds of movement and size on rates of encounter between members of the opposite sex, between gametes, between predators and prey, and between observers and the individuals that they are counting. One limitation of published models has been that they predict rates of encounter, but give no means of determining whether observations differ significantly from predictions. Another uncertainty is the robustness of the predictions when animal movements deviate from the model's assumptions in specific, biologically relevant ways. Here, we review applications of the ideal gas model, derive extensions of the model to cover some more realistic movement patterns, correct several errors that have arisen in the literature, and show how to generate confidence limits for expected rates of encounter among independently moving individuals. We illustrate these results using data from mangabey monkeys originally used along with the ideal gas model to argue that groups avoid each other. Although agent-based simulations provide a more flexible alternative approach, the ideal gas model remains both a valuable null model and a useful, less onerous, approximation to biological reality.
Blanchet Pierre J
Full Text Available Abstract Tardive dyskinesia remains an elusive and significant clinical entity that can possibly be understood via experimentation with animal models. We conducted a literature review on tardive dyskinesia modeling. Subchronic antipsychotic drug exposure is a standard approach to model tardive dyskinesia in rodents. Vacuous chewing movements constitute the most common pattern of expression of purposeless oral movements and represent an impermanent response, with individual and strain susceptibility differences. Transgenic mice are also used to address the contribution of adaptive and maladaptive signals induced during antipsychotic drug exposure. An emphasis on non-human primate modeling is proposed, and past experimental observations reviewed in various monkey species. Rodent and primate models are complementary, but the non-human primate model appears more convincingly similar to the human condition and better suited to address therapeutic issues against tardive dyskinesia.
Olengü, Nicholas O.; Reifman, Jaques
This paper explores how the accuracy of a first-principles physiological model can be enhanced by integrating data-driven, "black-box" models with the original model to form a "hybrid" model system. Both linear (autoregressive) and nonlinear (neural network) data-driven techniques are separately combined with a first-principles model to predict human body core temperature. Rectal core temperature data from nine volunteers, subject to four 30/10-minute cycles of moderate exercise/rest regimen in both CONTROL and HUMID environmental conditions, are used to develop and test the approach. The results show significant improvements in prediction accuracy, with average improvements of up to 30% for prediction horizons of 20 minutes. The models developed from one subject's data are also used in the prediction of another subject's core temperature. Initial results for this approach for a 20-minute horizon show no significant improvement over the first-principles model by itself.
Pinto, Carla M. A.; Santos, Alexandra P.
The study of locomotor patterns has been a major research goal in the last decades. Understanding how intralimb and interlimb coordination works out so well in animals' locomotion is a hard and challenging task. Many models have been proposed to model animal's rhythms. These models have also been applied to the control of rhythmic movements of adaptive legged robots, namely biped, quadruped and other designs. In this paper we study gait transition in a central pattern generator (CPG) model for bipeds, the 4-cells model. This model is proposed by Golubitsky, Stewart, Buono and Collins and is studied further by Pinto and Golubitsky. We briefly resume the work done by Pinto and Golubitsky. We compute numerically gait transition in the 4-cells CPG model for bipeds. We use Morris-Lecar equations and Wilson-Cowan equations as the internal dynamics for each cell. We also consider two types of coupling between the cells: diffusive and synaptic. We obtain secondary gaits by bifurcation of primary gaits, by varying the coupling strengths. Nevertheless, some bifurcating branches could not be obtained, emphasizing the fact that despite analytically those bifurcations exist, finding them is a hard task and requires variation of other parameters of the equations. We note that the type of coupling did not influence the results.
Réus, Gislaine Z; Dos Santos, Maria Augusta B; Abelaira, Helena M; Quevedo, João
Anxiety disorders pose one of the largest threats to global mental health, and they predominantly emerge early in life. Social anxiety disorder, also known as social phobia, is the most common of all anxiety disorders. Moreover, it has severe consequences and is a disabling disorder that can cause an individual to be unable to perform the tasks of daily life. Social anxiety disorder is associated with the subsequent development of major depression and other mental diseases, as well as increased substance abuse. Although some neurobiological alterations have been found to be associated with social anxiety disorder, little is known about this disorder. Animal models are useful tools for the investigation of this disorder, as well as for finding new pharmacological targets for treatment. Thus, this review will highlight the main animal models of anxiety associated with social phobia. Copyright © 2014 Elsevier Inc. All rights reserved.
Full Text Available Epidemiological studies report higher prevalence rates of stress-related disorders such as acute stress disorder and post-traumatic stress disorder (PTSD in women than in men following exposure to trauma. It is still not clear whether this greater prevalence in woman reflects a greater vulnerability to stress-related psychopathology. A number of individual and trauma-related characteristics have been hypothesized to contribute to these gender differences in physiological and psychological responses to trauma, differences in appraisal, interpretation or experience of threat, coping style or social support. In this context, the use of an animal model for PTSD to analyze some of these gender-related differences may be of particular utility. Animal models of PTSD offer the opportunity to distinguish between biological and socio-cultural factors, which so often enter the discussion about gender differences in PTSD prevalence.
Czéh, Boldizsár; Fuchs, Eberhard; Flügge, Gabriele
Numerous clinical evidences support the notion that glial changes in fronto-limbic brain areas could contribute to the pathophysiology of mood disorders. Glial alterations have been reported not only in patients, but also in various kinds of animal models for depression. Molecular and cellular data suggest that all the major classes of glial cells are affected in these conditions, including astrocytes, oligodendrocytes, NG2-positive cells and microglia. The aim of this review was to summarize the currently available experimental results demonstrating alterations in glial morphology and functioning in animal models for mood disorders. Better understanding of these glial changes affecting neuronal activity could help us to identify novel targets for the development of antidepressant drugs.
Alexandre M. Lehnen
Full Text Available Metabolic syndrome has been defined as a group of risk factors that directly contribute to the development of cardiovascular disease and/or type 2 diabetes. Insulin resistance seems to have a fundamental role in the genesis of this syndrome. Over the past years to the present day, basic and translational research has used small animal models to explore the pathophysiology of metabolic syndrome and to develop novel therapies that might slow the progression of this prevalent condition. In this paper we discuss the animal models used for the study of metabolic syndrome, with particular focus on cardiovascular changes, since they are the main cause of death associated with the condition in humans.
Plant, Malcolm; van Schaik, Paul; Gullone, Eleonora; Flynn, Clifton
Whereas the majority of previous research conducted on animal abuse has been in environments where animal abuse is rarely evidenced, the current study investigated the ramifications of animal abuse in an environment wherein the national culture creates an ethos of the "social acceptability" of animal abuse in society. Two survey studies were conducted with adolescent participants, to investigate the role played by several factors in the prediction of animal abuse in this age group. In Study 1, with samples from two different national cultures (101 from Germany and 169 from Romania; 143 boys/135 girls; age 13 to 17), animal abuse was negatively associated with affective empathy and national culture; more frequent animal abuse was found in Romania. Affective empathy fully mediated the association between gender and animal abuse. Specifically, girls were found to be higher in affective empathy; in turn, participants who were higher in affective empathy committed less animal abuse. Witnessing animal abuse was also predictive of engaging in animal abuse, but not independent of national culture. In Study 2, 15-year-old males ( n = 21) and females ( n = 39) took part, 29 from rural and 31 from urban locations in Romania. Rural adolescents were more likely to abuse animals and had higher exposure to domestic violence, which (in turn) was associated with more animal abuse. The implications of these findings in a society where animal abuse is encouraged and enacted on a national scale are discussed.
In the study the contamination of domestic animal products (milk, beef, pork) and grain is predicted applying a compartment model approach to simulate the dynamic behaviour of radionuclides in the biosphere after an accidental atmospheric deposition. Further, the radionuclide intakes into human body by consumption of the contaminated domestic animal products and the arising internal doses, are studied. The contamination of domestic animal products and grain are predicted by considering three representative deposition cases. The considered deposition timepoints are: spring (1st of May), summer (1st of July) and autumn (1st of September). The nuclides considered are 137 Cs, 134 Cs and 90 Sr. (18 refs., 14 figs., 8 tabs.)
Godar, Sean C; Mosher, Laura J; Di Giovanni, Giuseppe; Bortolato, Marco
Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders. Copyright © 2014 Elsevier B.V. All rights reserved.
Sugiyama, Naoto; Nishiyama, Eiji; Nishikawa, Yukitoshi; Sasamura, Takashi; Nakade, Shinji; Okawa, Katsumasa; Nagasawa, Tadashi; Yuki, Akane
Patients who have an ischemic stroke are at high risk of swallowing disorders. Aspiration due to swallowing disorders, specifically delayed trigger of the pharyngeal stage of swallowing, predisposes such patients to pneumonia. In the present study, we evaluated swallowing reflex in a rat model of transient middle cerebral artery occlusion (tMCAO), which is one of the most common experimental animal models of cerebral ischemia, in order to develop a novel animal model of dysphagia following ischemic stroke. A swallowing reflex was elicited by a 10-s infusion of distilled water (DW) to the pharyngolaryngeal region in the tMCAO rat model. Swallowing reflex was estimated using the electromyographic activity of the mylohyoid muscle from 1 to 3 weeks after surgery. Two weeks after tMCAO, the number of swallows significantly decreased and the onset latency of the first swallow was prolonged compared with that of the sham group. The number of swallows in rats significantly increased by infusions of 10 mM citric acid and 0.6 μM capsaicin to the pharyngolaryngeal region compared with the number from infusion of DW. It has been reported that sensory stimulation of the pharyngolaryngeal region with citric acid, capsaicin, and L-menthol ameliorates hypofunction of pharyngeal-stage swallowing in dysphagia patients. Therefore, the tMCAO rat model may show some of the symptoms of pharyngeal-stage swallowing disorders, similar to those in patients with ischemic stroke. This rat tMCAO model has the potential to become a novel animal model of dysphagia following stroke that is useful for development of therapeutic methods and drugs.
De la Haba, Maria José; Garrido-Varo, Ana; Guerrero-Ginel, José Emilio; Pérez-Marín, Dolores C
Near-infrared calibrations were developed for the instantaneous prediction of amino acids composition of processed animal proteins (PAPs). Two sample presentation modes were compared (ground vs intact) for demonstrating the viability of the analysis in the intact form, avoiding the need for milling. Modified partial least-squares (MPLS) equations for the prediction of amino acids in PAPs were developed using the same set of samples (N = 92 PAPs) analyzed in ground and intact form and in three cups differing in the optical window size. The standard error for cross validation (SECV) and the coefficient of determination (1-VR) values yielded with the calibrations developed using the samples analyzed in the intact form showed similar or even better accuracy than those obtained with finely ground samples. The excellent predictive ability (1-VR > 0.90; CV marketing of these important protein feed ingredients, alleviating the costs and time associated with the routine quality controls.
Full Text Available One segment of the population that is particularly inclined to liver fat accumulation is postmenopausal women. Although nonalcoholic hepatic steatosis is more common in men than in women, after menopause there is a reversal in gender distribution. At the present time, weight loss and exercise are regarded as first line treatments for NAFLD in postmenopausal women, as it is the case for the management of metabolic syndrome. In recent years, there has been substantial evidence coming mostly from the use of the animal model, that indeed estrogens withdrawal is associated with modifications of molecular markers favouring the activity of metabolic pathways ultimately leading to liver fat accumulation. In addition, the use of the animal model has provided physiological and molecular evidence that exercise training provides estrogens-like protective effects on liver fat accumulation and its consequences. The purpose of the present paper is to present information relative to the development of a state of NAFLD resulting from the absence of estrogens and the role of exercise training, emphasizing on the contribution of the animal model on these issues.
Srour, Nadim; Thébaud, Bernard
Asthma control frequently falls short of the goals set in international guidelines. Treatment options for patients with poorly controlled asthma despite inhaled corticosteroids and long-acting β-agonists are limited, and new therapeutic options are needed. Stem cell therapy is promising for a variety of disorders but there has been no human clinical trial of stem cell therapy for asthma. We aimed to systematically review the literature regarding the potential benefits of stem cell therapy in animal models of asthma to determine whether a human trial is warranted. The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal asthma models. Nineteen studies were selected. They were found to be heterogeneous in their design. Mesenchymal stromal cells were used before sensitization with an allergen, before challenge with the allergen and after challenge, most frequently with ovalbumin, and mainly in BALB/c mice. Stem cell therapy resulted in a reduction of bronchoalveolar lavage fluid inflammation and eosinophilia as well as Th2 cytokines such as interleukin-4 and interleukin-5. Improvement in histopathology such as peribronchial and perivascular inflammation, epithelial thickness, goblet cell hyperplasia and smooth muscle layer thickening was universal. Several studies showed a reduction in airway hyper-responsiveness. Stem cell therapy decreases eosinophilic and Th2 inflammation and is effective in several phases of the allergic response in animal asthma models. Further study is warranted, up to human clinical trials. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
There have been many studies regarding the effectiveness of visual aids that go beyond that of static illustrations. Many of these have been concentrated on the effectiveness of visual aids such as animations and models or even non-traditional visual aid activities like role-playing activities. This study focuses on the effectiveness of three different types of visual aids: models, animation, and a role-playing activity. Students used a modeling kit made of Styrofoam balls and toothpicks to construct nucleotides and then bond nucleotides together to form DNA. Next, students created their own animation to depict the processes of DNA replication, transcription, and translation. Finally, students worked in teams to build proteins while acting out the process of translation. Students were given a pre- and post-test that measured their knowledge and comprehension of the four topics mentioned above. Results show that there was a significant gain in the post-test scores when compared to the pre-test scores. This indicates that the incorporated visual aids were effective methods for teaching DNA structure and processes.
Straka, Hans; Zwergal, Andreas; Cullen, Kathleen E
Our knowledge of the vestibular sensory system, its functional significance for gaze and posture stabilization, and its capability to ensure accurate spatial orientation perception and spatial navigation has greatly benefitted from experimental approaches using a variety of vertebrate species. This review summarizes the attempts to establish the roles of semicircular canal and otolith endorgans in these functions followed by an overview of the most relevant fields of vestibular research including major findings that have advanced our understanding of how this system exerts its influence on reflexive and cognitive challenges encountered during daily life. In particular, we highlight the contributions of different animal models and the advantage of using a comparative research approach. Cross-species comparisons have established that the morpho-physiological properties underlying vestibular signal processing are evolutionarily inherent, thereby disclosing general principles. Based on the documented success of this approach, we suggest that future research employing a balanced spectrum of standard animal models such as fish/frog, mouse and primate will optimize our progress in understanding vestibular processing in health and disease. Moreover, we propose that this should be further supplemented by research employing more "exotic" species that offer unique experimental access and/or have specific vestibular adaptations due to unusual locomotor capabilities or lifestyles. Taken together this strategy will expedite our understanding of the basic principles underlying vestibular computations to reveal relevant translational aspects. Accordingly, studies employing animal models are indispensible and even mandatory for the development of new treatments, medication and technical aids (implants) for patients with vestibular pathologies.
Lu Junliang; Yang Ning; Yang Jianping; Ma Junshan; Zhao Shijun
Objective: To find a way of establishing the model of acute massive pulmonary embolism in dog. Methods: Seven dogs were selected with self-clots made outside the body transferring through a 10 F guiding catheter into the central branch of pulmonary artery via the femoral vein approach on one side and then under pressure monitor of pulmonary artery until the very branch of pulmonary artery was occluded. Blood gas and pulmonary arterial pressure were tested before and after the embolization, Pulmonary artery pressure was continuously monitored together with the examinations of angiography. The bilateral lung specimens were resected for histological examination 12 hours in average after the embolization for comparative study. Results: One animal died of cardiogenic shock after clots injection; the other one presented with tachycardia and premature ventricular beat causing partial recanalization 12 h later. The others were occluded successfully in central branch of pulmonary artery and the pulmonary arterial pressure reached above 50 mmHg after occlusion. Pathologic examination showed the formation of red and mix thrombi within the vascular lumens. Conclusions: This method for making acute massive pulmonary embolism animal model was reliable, feasible and reproducible, and could provide an animal model of acute massive pulmonary embolism for other correlative experiments. (authors)
Browne, John A; Hensley, Christopher; McGuffee, Karen M
The goal of the current study was to examine the association between demographic characteristics and childhood experiences on the respondents' age of committing childhood animal cruelty and its recurrency. Using data collected from 257 male inmates at a Southern medium-security state prison, the current study seeks to replicate a study by Hensley, Tallichet, and Dutkiewicz. Results revealed that those respondents who were physically abused as children reported engaging in recurrent animal cruelty. The younger the age of respondent for first witnessing animal cruelty, the sooner his initiation to hurting and killing animals occurred. In addition, those who reported witnessing a parent commit acts of animal abuse reported that they committed animal abuse themselves at an older age, while those who witnessed a brother/sister commit animal abuse reported engaging in it at an earlier age. Therefore, physical abuse and witnessing primary socializers engage in animal abuse seem to be important in understanding the respondents' age of onset and repeated childhood animal cruelty.
Fahed, Robert; Raymond, Jean; Ducroux, Célina; Gentric, Jean-Christophe; Salazkin, Igor; Ziegler, Daniela; Gevry, Guylaine; Darsaut, Tim E
Flow diversion (FD) is increasingly used to treat intracranial aneurysms. We sought to systematically review published studies to assess the quality of reporting and summarize the results of FD in various animal models. Databases were searched to retrieve all animal studies on FD from 2000 to 2015. Extracted data included species and aneurysm models, aneurysm and neck dimensions, type of flow diverter, occlusion rates, and complications. Articles were evaluated using a checklist derived from the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Forty-two articles reporting the results of FD in nine different aneurysm models were included. The rabbit elastase-induced aneurysm model was the most commonly used, with 3-month occlusion rates of 73.5%, (95%CI [61.9-82.6%]). FD of surgical sidewall aneurysms, constructed in rabbits or canines, resulted in high occlusion rates (100% [65.5-100%]). FD resulted in modest occlusion rates (15.4% [8.9-25.1%]) when tested in six complex canine aneurysm models designed to reproduce more difficult clinical contexts (large necks, bifurcation, or fusiform aneurysms). Adverse events, including branch occlusion, were rarely reported. There were no hemorrhagic complications. Articles complied with 20.8 ± 3.9 of 41 ARRIVE items; only a small number used randomization (3/42 articles [7.1%]) or a control group (13/42 articles [30.9%]). Preclinical studies on FD have shown various results. Occlusion of elastase-induced aneurysms was common after FD. The model is not challenging but standardized in many laboratories. Failures of FD can be reproduced in less standardized but more challenging surgical canine constructions. The quality of reporting could be improved.
Bélanger, Mireille; Butterworth, Roger F
The availability of adequate experimental models of acute liver failure (ALF) is of prime importance to provide a better understanding of this condition and allow the development and testing of new therapeutic approaches for patients with ALF. However, the numerous etiologies and complications of ALF contribute to the complexity of this condition and render the development of an ideal experimental model of ALF more difficult than expected. Instead, a number of different models that may be used for the study of specific aspects of ALF have been developed. The most common approaches used to induce ALFin experimental animals are surgical procedures, toxic liver injury,or a combination of both. Despite the high prevalence of viral hepatitis worldwide, very few satisfactory viral models of ALF are available. Established and newly developed models of ALF are reviewed.
Collective decision-making plays a central part in the lives of many social animals. Two important factors that influence collective decision-making are information uncertainty and conflicting preferences. Here, I bring together, and briefly review, basic models relating to animal collective decision-making in situations with information uncertainty and in situations with conflicting preferences between group members. The intention is to give an overview about the different types of modelling approaches that have been employed and the questions that they address and raise. Despite the use of a wide range of different modelling techniques, results show a coherent picture, as follows. Relatively simple cognitive mechanisms can lead to effective information pooling. Groups often face a trade-off between decision accuracy and speed, but appropriate fine-tuning of behavioural parameters could achieve high accuracy while maintaining reasonable speed. The right balance of interdependence and independence between animals is crucial for maintaining group cohesion and achieving high decision accuracy. In conflict situations, a high degree of decision-sharing between individuals is predicted, as well as transient leadership and leadership according to needs and physiological status. Animals often face crucial trade-offs between maintaining group cohesion and influencing the decision outcome in their own favour. Despite the great progress that has been made, there remains one big gap in our knowledge: how do animals make collective decisions in situations when information uncertainty and conflict of interest operate simultaneously?
Murphy, Daniel L.; Gaertner, Matthew N.
This study evaluates four growth prediction models--projection, student growth percentile, trajectory, and transition table--commonly used to forecast (and give schools credit for) middle school students' future proficiency. Analyses focused on vertically scaled summative mathematics assessments, and two performance standards conditions (high…
For the first time, a textbook that brings together classical predictive control with treatment of up-to-date robust and stochastic techniques. Model Predictive Control describes the development of tractable algorithms for uncertain, stochastic, constrained systems. The starting point is classical predictive control and the appropriate formulation of performance objectives and constraints to provide guarantees of closed-loop stability and performance. Moving on to robust predictive control, the text explains how similar guarantees may be obtained for cases in which the model describing the system dynamics is subject to additive disturbances and parametric uncertainties. Open- and closed-loop optimization are considered and the state of the art in computationally tractable methods based on uncertainty tubes presented for systems with additive model uncertainty. Finally, the tube framework is also applied to model predictive control problems involving hard or probabilistic constraints for the cases of multiplic...
Lee Sang Min
Full Text Available Abstract Amyotrophic lateral sclerosis (ALS is a paralyzing disorder characterized by the progressive degeneration and death of motor neurons and occurs both as a sporadic and familial disease. Mutant SOD1 (mtSOD1 in motor neurons induces vulnerability to the disease through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, defective axonal transport- and growth factor signaling, excitotoxicity, and neuro-inflammation. Melittin is a 26 amino acid protein and is one of the components of bee venom which is used in traditional Chinese medicine to inhibit of cancer cell proliferation and is known to have anti-inflammatory and anti-arthritic effects. The purpose of the present study was to determine if melittin could suppress motor neuron loss and protein misfolding in the hSOD1G93A mouse, which is commonly used as a model for inherited ALS. Meltittin was injected at the 'ZuSanLi' (ST36 acupuncture point in the hSOD1G93A animal model. Melittin-treated animals showed a decrease in the number of microglia and in the expression level of phospho-p38 in the spinal cord and brainstem. Interestingly, melittin treatment in symptomatic ALS animals improved motor function and reduced the level of neuron death in the spinal cord when compared to the control group. Furthermore, we found increased of α-synuclein modifications, such as phosphorylation or nitration, in both the brainstem and spinal cord in hSOD1G93A mice. However, melittin treatment reduced α-synuclein misfolding and restored the proteasomal activity in the brainstem and spinal cord of symptomatic hSOD1G93A transgenic mice. Our research suggests a potential functional link between melittin and the inhibition of neuroinflammation in an ALS animal model.
Sangild, Per Torp; Ney, Denise M; Sigalet, David L
help but careful evaluation of the cellular mechanisms, safety and translational relevance of new procedures are required. Distal intestinal resection, without a functioning colon, results in the most severe complications and adaptation may depend on the age at resection (preterm, term, young, adult...... hormone, insulin-like growth factor 1, epidermal growth factor, keratinocyte growth factor). The greater size of rats, and especially young pigs, is an advantage for testing surgical procedures and nutritional interventions (e.g. PN, milk diets, long/short chain lipids, pre- and probiotics). Conversely......, newborn pigs and weanling rats represent a translational advantage for infant SBS due to their immature intestine. A balance among practical, economical, experimental and ethical constraints determines the choice of SBS model for each clinical or basic research question....
A valid animal model of depression was used to explore specific adrenergic receptor differences between rats exhibiting aberrant behavior and control groups. Preliminary experiments revealed a distinct upregulation of hippocampal beta-receptors (as compared to other brain regions) in those animals acquiring a response deficit as a result of exposure to inescapable footshock. Concurrent studies using standard receptor binding techniques showed no large changes in the density of alpha-adrenergic, serotonergic, or dopaminergic receptor densities. This led to the hypothesis that the hippocampal beta-receptor in responses deficient animals could be correlated with the behavioral changes seen after exposure to the aversive stimulus. Normalization of the behavior through the administration of antidepressants could be expected to reverse the biochemical changes if these are related to the mechanism of action of antidepressant drugs. This study makes three important points: (1) there is a relevant biochemical change in the hippocampus of response deficient rats which occurs in parallel to a well-defined behavior, (2) the biochemical and behavioral changes are normalized by antidepressant treatments exhibiting both serotonergic and adrenergic mechanisms of action, and (3) the mode of action of antidepressants in this model is probably a combination of serotonergic and adrenergic influences modulating the hippocampal beta-receptor. These results are discussed in relation to anatomical and biochemical aspects of antidepressant action
Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A
Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long
Alaminos, David; Del Castillo, Agustín; Fernández, Manuel Ángel
The recent world financial crisis has increased the number of bankruptcies in numerous countries and has resulted in a new area of research which responds to the need to predict this phenomenon, not only at the level of individual countries, but also at a global level, offering explanations of the common characteristics shared by the affected companies. Nevertheless, few studies focus on the prediction of bankruptcies globally. In order to compensate for this lack of empirical literature, this study has used a methodological framework of logistic regression to construct predictive bankruptcy models for Asia, Europe and America, and other global models for the whole world. The objective is to construct a global model with a high capacity for predicting bankruptcy in any region of the world. The results obtained have allowed us to confirm the superiority of the global model in comparison to regional models over periods of up to three years prior to bankruptcy.
Galanopoulou, Aristea S.
Infantile spasms are age-specific seizures of infantile epileptic encephalopathies that are usually associated with poor epilepsy and neurodevelopmental outcomes. The current treatments are not always effective and may be associated with significant side effects. Various mechanisms have been proposed as pathogenic for infantile spasms, including cortical or brainstem dysfunction, disruption of normal cortical-subcortical communications, genetic defects, inflammation, stress, developmental abnormalities. Many of these have been recently tested experimentally, resulting into the emergence of several animal models of infantile spasms. The stress theory of spasms yielded the corticotropin releasing hormone (CRH) induced model, which showed the higher proconvulsant potency of CRH in developing rats, although only limbic seizures were observed. Models of acute induction of infantile spasms in rodents include the N-methyl-D-aspartate (NMDA) model of emprosthotonic seizures, the prenatal betamethasone and prenatal stress variants of the NMDA model, and the γ-butyrolactone induced spasms in a Down’s syndrome mouse model. Chronic rodent models of infantile spasms include the tetrodotoxin model and the multiple-hit models in rats, as well as two genetic mouse models of interneuronopathies with infantile spasms due to loss of function of the aristaless X-linked homeobox related gene (ARX). This review discusses the emerging mechanisms for generation of infantile spasms and their associated chronic epileptic and dyscognitive phenotype as well as the recent progress in identifying pathways to better treat this epileptic encephalopathy. PMID:23312951
Oliveira, Erick da S.; Junior, Alberico B. de C.
The numerical dosimetry uses virtual anthropomorphic simulators to represent the human being in computational framework and thus assess the risks associated with exposure to a radioactive source. With the development of computer animation software, the development of these simulators was facilitated using only knowledge of human anatomy to prepare various types of simulators (man, woman, child and baby) in various positions (sitting, standing, running) or part thereof (head, trunk and limbs). These simulators are constructed by loops of handling and due to the versatility of the method, one can create various geometries irradiation was not possible before. In this work, we have built an exhibition of a radiopharmaceutical scenario manipulating radioactive material using animation software and graphical modeling and anatomical database. (author)
Ayhan, Yavuz; Sawa, Akira; Ross, Christopher A; Pletnikov, Mikhail V
The pathogenesis of schizophrenia and related mental illnesses likely involves multiple interactions between susceptibility genes of small effects and environmental factors. Gene-environment interactions occur across different stages of neurodevelopment to produce heterogeneous clinical and pathological manifestations of the disease. The main obstacle for mechanistic studies of gene-environment interplay has been the paucity of appropriate experimental systems for elucidating the molecular pathways that mediate gene-environment interactions relevant to schizophrenia. Recent advances in psychiatric genetics and a plethora of experimental data from animal studies allow us to suggest a new approach to gene-environment interactions in schizophrenia. We propose that animal models based on identified genetic mutations and measurable environment factors will help advance studies of the molecular mechanisms of gene-environment interplay.
Brooks, Elizabeth D; Koeberl, Dwight D
Glycogen storage diseases (GSD), a unique category of inherited metabolic disorders, were first described early in the twentieth century. Since then, the biochemical and genetic bases of these disorders have been determined, and an increasing number of animal models for GSD have become available. At least seven large mammalian models have been developed for laboratory research on GSDs. These models have facilitated the development of new therapies, including gene therapy, which are undergoing clinical translation. For example, gene therapy prolonged survival and prevented hypoglycemia during fasting for greater than one year in dogs with GSD type Ia, and the need for periodic re-administration to maintain efficacy was demonstrated in that dog model. The further development of gene therapy could provide curative therapy for patients with GSD and other inherited metabolic disorders.
Lee, Chew K; Chang, Choong C; Johor, Asmah; Othman, Puwira; Baba, Roshidah
Hand dermatitis associated fingerprint changes is a significant problem and affects fingerprint verification processes. This study was done to develop a clinically useful prediction model for fingerprint verification in patients with hand dermatitis. A case-control study involving 100 patients with hand dermatitis. All patients verified their thumbprints against their identity card. Registered fingerprints were randomized into a model derivation and model validation group. Predictive model was derived using multiple logistic regression. Validation was done using the goodness-of-fit test. The fingerprint verification prediction model consists of a major criterion (fingerprint dystrophy area of ≥ 25%) and two minor criteria (long horizontal lines and long vertical lines). The presence of the major criterion predicts it will almost always fail verification, while presence of both minor criteria and presence of one minor criterion predict high and low risk of fingerprint verification failure, respectively. When none of the criteria are met, the fingerprint almost always passes the verification. The area under the receiver operating characteristic curve was 0.937, and the goodness-of-fit test showed agreement between the observed and expected number (P = 0.26). The derived fingerprint verification failure prediction model is validated and highly discriminatory in predicting risk of fingerprint verification in patients with hand dermatitis. © 2014 The International Society of Dermatology.
R is fast becoming the lingua franca for analyzing data via statistics, visualization, and predictive analytics. For enterprise-scale data, R users have three main concerns: scalability, performance, and production deployment. Oracle's R-based technologies - Oracle R Distribution, Oracle R Enterprise, Oracle R Connector for Hadoop, and the R package ROracle - address these concerns. In this talk, we introduce Oracle's R technologies, highlighting how each enables R users to achieve scalability and performance while making production deployment of R results a natural outcome of the data analyst/scientist efforts. The focus then turns to Oracle R Enterprise with code examples using the transparency layer and embedded R execution, targeting massive predictive modeling. One goal behind massive predictive modeling is to build models per entity, such as customers, zip codes, simulations, in an effort to understand behavior and tailor predictions at the entity level. Predictions...
Full Text Available The animal model of the whole-size and reduced-size liver transplantation in both rat and mouse has been successfully established. Because of the difficulties and complexities in microsurgical technology, the animal model of dual liver transplantation was still not established for twelve years since the first human dual liver transplantation has been made a success. There is an essential need to establish this animal model to lay a basic foundation for clinical practice. To study the physiological and histopathological changes of dual liver transplantation, "Y" type vein from the cross part between vena cava and two iliac of donor and "Y' type prosthesis were employed to recanalize portal vein and the bile duct between dual liver grafts and recipient. The dual right upper lobes about 45-50% of the recipient liver volume were taken as donor, one was orthotopically implanted at its original position, the other was rotated 180° sagitally and heterotopically positioned in the left upper quadrant. Microcirculation parameters, liver function, immunohistochemistry and survival were analyzed to evaluate the function of dual liver grafts. No significant difference in the hepatic microcirculatory flow was found between two grafts in the first 90 minutes after reperfusion. Light and electronic microscope showed the liver architecture was maintained without obvious features of cellular destruction and the continuity of the endothelium was preserved. Only 3 heterotopically positioned graft appeared patchy desquamation of endothelial cell, mitochondrial swelling and hepatocytes cytoplasmic vacuolization. Immunohistochemistry revealed there is no difference in hepatocyte activity and the ability of endothelia to contract and relax after reperfusion between dual grafts. Dual grafts made a rapid amelioration of liver function after reperfusion. 7 rats survived more than 7 days with survival rate of 58.3.%. Using "Y" type vein and bile duct prosthesis, we
Cunha, Gerald R; Sinclair, Adriane; Risbridger, Gail; Hutson, John; Baskin, Laurence S
Hypospadias is a congenital abnormality of the penile urethra with an incidence of approximately 1:200-1:300 male births, which has doubled over the past three decades. The aetiology of the overwhelming majority of hypospadias remains unknown but appears to be a combination of genetic susceptibility and prenatal exposure to endocrine disruptors. Reliable animal models of hypospadias are required for better understanding of the mechanisms of normal penile urethral formation and hence hypospadias. Mice and/or rats are generally used for experimental modelling of hypospadias, however these do not fully reflect the human condition. To use these models successfully, researchers must understand the similarities and differences between mouse, rat and human penile anatomy as well as the normal morphogenetic mechanisms of penile development in these species. Despite some important differences, numerous features of animal and human hypospadias are shared: the prevalence of distal penile malformations; disruption of the urethral meatus; disruption of urethra-associated erectile bodies; and a common mechanism of impaired epithelial fusion events. Rat and mouse models of hypospadias are crucial to our understanding of hypospadias to ultimately reduce its incidence through better preventive strategies.
Nihar Ranjan Jana
Full Text Available Angelman syndrome (AS is a neurodevelopmental disorder characterized by severe mental retardation, lack of speech, ataxia, susceptibility to seizures, and unique behavioral features such as easily provoked smiling and laughter and autistic features. The disease is primarily caused by deletion or loss-of-function mutations of the maternally inherited UBE3A gene located within chromosome 15q11-q13. The UBE3A gene encodes a 100 kDa protein that functions as ubiquitin ligase and transcriptional coactivator. Emerging evidence now indicates that UBE3A plays a very important role in synaptic function and in regulation of activity-dependent synaptic plasticity. A number of animal models for AS have been generated to understand the disease pathogenesis. The most widely used model is the UBE3A-maternal-deficient mouse that recapitulates most of the essential features of AS including cognitive and motor abnormalities. This paper mainly discusses various animal models of AS and how these models provide fundamental insight into understanding the disease biology for potential therapeutic intervention.
Jana, Nihar Ranjan
Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe mental retardation, lack of speech, ataxia, susceptibility to seizures, and unique behavioral features such as easily provoked smiling and laughter and autistic features. The disease is primarily caused by deletion or loss-of-function mutations of the maternally inherited UBE3A gene located within chromosome 15q11-q13. The UBE3A gene encodes a 100 kDa protein that functions as ubiquitin ligase and transcriptional coactivator. Emerging evidence now indicates that UBE3A plays a very important role in synaptic function and in regulation of activity-dependent synaptic plasticity. A number of animal models for AS have been generated to understand the disease pathogenesis. The most widely used model is the UBE3A-maternal-deficient mouse that recapitulates most of the essential features of AS including cognitive and motor abnormalities. This paper mainly discusses various animal models of AS and how these models provide fundamental insight into understanding the disease biology for potential therapeutic intervention. PMID:22830052
Developing statistical models that estimate the probability of testicular cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.
Developing statistical models that estimate the probability of developing pancreatic cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.
Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.
Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.
Developing statistical models that estimate the probability of developing bladder cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.
Developing statistical models that estimate the probability of developing esophageal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.
Developing statistical models that estimate the probability of developing cervical cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.
Developing statistical models that estimate the probability of developing breast cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.
Developing statistical models that estimate the probability of developing lung cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.
Developing statistical models that estimate the probability of developing liver cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.
Developing statistical models that estimate the probability of developing ovarian cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.
This simulation study compared the utility of various discrepancy measures within a posterior predictive model checking (PPMC) framework for detecting different types of data-model misfit in multidimensional Bayesian network (BN) models. The investigated conditions were motivated by an applied research program utilizing an operational complex…
Nowik, N; Podlasz, P; Jakimiuk, A; Kasica, N; Sienkiewicz, W; Kaleczyc, J
The zebrafish (Danio rerio) has become known as an excellent model organism for studies of vertebrate biology, vertebrate genetics, embryonal development, diseases and drug screening. Nevertheless, there is still lack of detailed reports about usage of the zebrafish as a model in veterinary medicine. Comparing to other vertebrates, they can lay hundreds of eggs at weekly intervals, externally fertilized zebrafish embryos are accessible to observation and manipulation at all stages of their development, which makes possible to simplify the research techniques such as fate mapping, fluorescent tracer time-lapse lineage analysis and single cell transplantation. Although zebrafish are only 2.5 cm long, they are easy to maintain. Intraperitoneal and intracerebroventricular injections, blood sampling and measurement of food intake are possible to be carry out in adult zebrafish. Danio rerio is a useful animal model for neurobiology, developmental biology, drug research, virology, microbiology and genetics. A lot of diseases, for which the zebrafish is a perfect model organism, affect aquatic animals. For a part of them, like those caused by Mycobacterium marinum or Pseudoloma neutrophila, Danio rerio is a natural host, but the zebrafish is also susceptible to the most of fish diseases including Itch, Spring viraemia of carp and Infectious spleen and kidney necrosis. The zebrafish is commonly used in research of bacterial virulence. The zebrafish embryo allows for rapid, non-invasive and real time analysis of bacterial infections in a vertebrate host. Plenty of common pathogens can be examined using zebrafish model: Streptococcus iniae, Vibrio anguillarum or Listeria monocytogenes. The steps are taken to use the zebrafish also in fungal research, especially that dealing with Candida albicans and Cryptococcus neoformans. Although, the zebrafish is used commonly as an animal model to study diseases caused by external agents, it is also useful in studies of metabolic
Knippels, Leon M.J.; Penninks, Andre H.
The potential allergenicity of newly introduced proteins in genetically engineered foods has become an important safety evaluation issue. However, to evaluate the potential allergenicity and the potency of new proteins in our food, there are still no widely accepted and reliable test systems. The best-known allergy assessment proposal for foods derived from genetically engineered plants was the careful stepwise process presented in the so-called ILSI/IFBC decision tree. A revision of this decision tree strategy was proposed by a FAO/WHO expert consultation. As prediction of the sensitizing potential of the novel introduced protein based on animal testing was considered to be very important, animal models were introduced as one of the new test items, despite the fact that non of the currently studied models has been widely accepted and validated yet. In this paper, recent results are summarized of promising models developed in rat and mouse
Westhof, Eric; Masquida, Benoît; Jossinet, Fabrice
SUMMARY A general approach for modeling the architecture of large and structured RNA molecules is described. The method exploits the modularity and the hierarchical folding of RNA architecture that is viewed as the assembly of preformed double-stranded helices defined by Watson-Crick base pairs and RNA modules maintained by non-Watson-Crick base pairs. Despite the extensive molecular neutrality observed in RNA structures, specificity in RNA folding is achieved through global constraints like lengths of helices, coaxiality of helical stacks, and structures adopted at the junctions of helices. The Assemble integrated suite of computer tools allows for sequence and structure analysis as well as interactive modeling by homology or ab initio assembly with possibilities for fitting within electronic density maps. The local key role of non-Watson-Crick pairs guides RNA architecture formation and offers metrics for assessing the accuracy of three-dimensional models in a more useful way than usual root mean square deviation (RMSD) values. PMID:20504963
Miller, Laura A.; Goldman, Daniel I.; Hedrick, Tyson L.; Tytell, Eric D.; Wang, Z. Jane; Yen, Jeannette; Alben, Silas
Recent advances in computational methods have made realistic large-scale simulations of animal locomotion possible. This has resulted in numerous mathematical and computational studies of animal movement through fluids and over substrates with the purpose of better understanding organisms’ performance and improving the design of vehicles moving through air and water and on land. This work has also motivated the development of improved numerical methods and modeling techniques for animal locomotion that is characterized by the interactions of fluids, substrates, and structures. Despite the large body of recent work in this area, the application of mathematical and numerical methods to improve our understanding of organisms in the context of their environment and physiology has remained relatively unexplored. Nature has evolved a wide variety of fascinating mechanisms of locomotion that exploit the properties of complex materials and fluids, but only recently are the mathematical, computational, and robotic tools available to rigorously compare the relative advantages and disadvantages of different methods of locomotion in variable environments. Similarly, advances in computational physiology have only recently allowed investigators to explore how changes at the molecular, cellular, and tissue levels might lead to changes in performance at the organismal level. In this article, we highlight recent examples of how computational, mathematical, and experimental tools can be combined to ultimately answer the questions posed in one of the grand challenges in organismal biology: “Integrating living and physical systems.” PMID:22988026
García-Curbelo, Yanelys; Bocourt, Ramón; Savón, Lourdes L; García-Vieyra, Maria Isabel; López, Mercedes G
The use of prebiotics such as fructans has increased in human and animal nutrition because of their productive performance and health benefits. Agave fourcroydes has shown high concentrations of fructans in their stems; however, there is no information on new products derived from this plant that might enhance its added value. Therefore, we evaluated the prebiotic effect of Agave fourcroydes fructans in an animal model. Male mice (C57BL/6J) were fed on parallel form with a standard diet or diets supplemented with 10% of fructans from Cichorium intybus (Raftilose P95) and Agave fourcroydes from Cuba for 35 days. The body weight, food intake, blood glucose, triglycerides and cholesterol, gastrointestinal organ weights, fermentation indicators in cecal and colon contents and mineral content in femurs were determined. The body weight and food intake of mice were not significantly modified by any treatment. However, serum glucose, cholesterol and triglycerides decreased (P Agave fourcroydes in the mice diet induced a prebiotic response, similar to or greater than the commercial product (Raftilose P95) and this constitutes a promising alternative with potential use not only in animal but also in human diets.
Miller, Laura A; Goldman, Daniel I; Hedrick, Tyson L; Tytell, Eric D; Wang, Z Jane; Yen, Jeannette; Alben, Silas
Recent advances in computational methods have made realistic large-scale simulations of animal locomotion possible. This has resulted in numerous mathematical and computational studies of animal movement through fluids and over substrates with the purpose of better understanding organisms' performance and improving the design of vehicles moving through air and water and on land. This work has also motivated the development of improved numerical methods and modeling techniques for animal locomotion that is characterized by the interactions of fluids, substrates, and structures. Despite the large body of recent work in this area, the application of mathematical and numerical methods to improve our understanding of organisms in the context of their environment and physiology has remained relatively unexplored. Nature has evolved a wide variety of fascinating mechanisms of locomotion that exploit the properties of complex materials and fluids, but only recently are the mathematical, computational, and robotic tools available to rigorously compare the relative advantages and disadvantages of different methods of locomotion in variable environments. Similarly, advances in computational physiology have only recently allowed investigators to explore how changes at the molecular, cellular, and tissue levels might lead to changes in performance at the organismal level. In this article, we highlight recent examples of how computational, mathematical, and experimental tools can be combined to ultimately answer the questions posed in one of the grand challenges in organismal biology: "Integrating living and physical systems."
Zhang, Qinghua; Ljung, Lennart
NLARX (NonLinear AutoRegressive with eXogenous inputs) models are frequently used in black-box nonlinear system identication. Though it is easy to make one step ahead prediction with such models, multiple steps prediction is far from trivial. The main difficulty is that in general there is no easy way to compute the mathematical expectation of an output conditioned by past measurements. An optimal solution would require intensive numerical computations related to nonlinear filltering. The pur...
Fernandez-Miranda, J C; Barges-Coll, J; Prevedello, D M; Engh, J; Snyderman, C; Carrau, R; Gardner, P A; Kassam, A B
The learning curve for endonasal endoscopic and neuroendoscopic port surgery is long and often associated with an increase in complication rates as surgeons gain experience. We present an animal model for laboratory training aiming to encourage the young generation of neurosurgeons to pursue proficiency in endoscopic neurosurgical techniques. 20 Wistar rats were used as models. The animals were introduced into a physical trainer with multiple ports to carry out fully endoscopic microsurgical procedures. The vertical and horizontal dimensions of the paired ports (simulated nostrils) were: 35×20 mm, 35×15 mm, 25×15 mm, and 25×10 mm. 2 additional single 11.5 mm endoscopic ports were added. Surgical depth varied as desired between 8 and 15 cm. The cervical and abdominal regions were the focus of the endoscopic microsurgical exercises. The different endoscopic neurosurgical techniques were effectively trained at the millimetric dimension. Levels of progressive surgical difficulty depending upon the endoneurosurgical skills set needed for a particular surgical exercise were distinguished. LEVEL 1 is soft-tissue microdissection (exposure of cervical muscular plane and retroperitoneal space); LEVEL 2 is soft-tissue-vascular and vascular-capsule microdissection (aorto-cava exposure, carotid sheath opening, external jugular vein isolation); LEVEL 3 is artery-nerve microdissection (carotid-vagal separation); LEVEL 4 is artery-vein microdissection (aorto-cava separation); LEVEL 5 is vascular repair and microsuturing (aortic rupture), which verified the lack of current proper instrumentation. The animal training model presented here has the potential to shorten the length of the learning curve in endonasal endoscopic and neuroendoscopic port surgery and reduce the incidence of training-related surgical complications. © Georg Thieme Verlag KG Stuttgart · New York.
A. E. Sterk
Full Text Available Extreme value theory in deterministic systems is concerned with unlikely large (or small values of an observable evaluated along evolutions of the system. In this paper we study the finite-time predictability of extreme values, such as convection, energy, and wind speeds, in three geophysical models. We study whether finite-time Lyapunov exponents are larger or smaller for initial conditions leading to extremes. General statements on whether extreme values are better or less predictable are not possible: the predictability of extreme values depends on the observable, the attractor of the system, and the prediction lead time.
Reynolds, Clare M; Vickers, Mark H
Any effective strategy to tackle the global obesity and rising noncommunicable disease epidemic requires an in-depth understanding of the mechanisms that underlie these conditions that manifest as a consequence of complex gene-environment interactions. In this context, it is now well established that alterations in the early life environment, including suboptimal nutrition, can result in an increased risk for a range of metabolic, cardiovascular, and behavioral disorders in later life, a process preferentially termed developmental programming. To date, most of the mechanistic knowledge around the processes underpinning development programming has been derived from preclinical research performed mostly, but not exclusively, in laboratory mouse and rat strains. This review will cover the utility of small animal models in developmental programming, the limitations of such models, and potential future directions that are required to fully maximize information derived from preclinical models in order to effectively translate to clinical use.
Marx, Alexander; Porubsky, Stefan; Belharazem, Djeda; Saruhan-Direskeneli, Güher; Schalke, Berthold; Ströbel, Philipp; Weis, Cleo-Aron
Thymoma-associated Myasthenia gravis (TAMG) is one of the anti-acetylcholine receptor MG (AChR-MG) subtypes. The clinico-pathological features of TAMG and its pathogenesis are described here in comparison with pathogenetic models suggested for the more common non-thymoma AChR-MG subtypes, early onset MG and late onset MG. Emphasis is put on the role of abnormal intratumorous T cell selection and activation, lack of intratumorous myoid cells and regulatory T cells as well as deficient expression of the autoimmune regulator (AIRE) by neoplastic thymic epithelial cells. We review spontaneous and genetically engineered thymoma models in a spectrum of animals and the extensive clinical and immunological overlap between canine, feline and human TAMG. Finally, limitations and perspectives of the transplantation of human and murine thymoma tissue into nude mice, as potential models for TAMG, are addressed. Copyright © 2015 Elsevier Inc. All rights reserved.
Mohammad Ali Saghiri
Full Text Available Background: Animal models have contributed to dental literature for several decades. The major aim of this review was to outline tooth development stages in mice, and attempt to addressing potential strain differences. A literature review was performed using electronic and hand-searching methods for the animal models in dentistry with special emphasis on mice and dentistry. Root canal development in both C57BL/6 and BALB/c strains were investigated. There are a number of published reports regarding the morphogenesis and molecular reaction and maturation stages of mice molars. We observed some similarity between the mice and human odontegeneis as primary factor for tooth development. Although mice may present some technical challenges, including the small size of the mouse molars, they have similar stages as humans for molar development, and can be used to monitor the effects of various biomaterials, regeneration, and remodeling. Thus, mice provide an ideal alternative model to study developmental and regenerative processes in dentistry.
Full Text Available Summary: Objective: Established preclinical disease models are essential for not only studying aetiology and/or pathophysiology of the relevant diseases but more importantly also for testing prevention and/or treatment concept(s. The present study proposed and established a detailed induction and assessment protocol for a unique and cost-effective preclinical steroid-associated osteonecrosis (SAON in rats with pulsed injections of lipopolysaccharide (LPS and methylprednisolone (MPS. Methods: Sixteen 24-week-old male Sprague–Dawley rats were used to induce SAON by one intravenous injection of LPS (0.2 mg/kg and three intraperitoneal injections of MPS (100 mg/kg with a time interval of 24 hour, and then, MPS (40 mg/kg was intraperitoneally injected three times a week from week 2 until sacrifice. Additional 12 rats were used as normal controls. Two and six weeks after induction, animals were scanned by metabolic dual energy X-ray absorptiometry for evaluation of tissue composition; serum was collected for bone turnover markers, Microfil perfusion was performed for angiography, the liver was collected for histopathology and bilateral femora and bilateral tibiae were collected for histological examination. Results: Three rats died after LPS injection, i.e., with 15.8% (3/19 mortality. Histological evaluation showed 100% incidence of SAON at week 2. Dual energy X-ray absorptiometry showed significantly higher fat percent and lower lean mass in SAON group at week 6. Micro-computed tomography (Micro-CT showed significant bone degradation at proximal tibia 6 weeks after SAON induction. Angiography illustrated significantly less blood vessels in the proximal tibia and significantly more leakage particles in the distal tibia 2 weeks after SAON induction. Serum amino-terminal propeptide of type I collagen and osteocalcin were significantly lower at both 2 and 6 weeks after SAON induction, and serum carboxy-terminal telopeptide was significantly
Schoups, G.; van de Giesen, N. C.; Savenije, H. H. G.
A common concern in hydrologic modeling is overparameterization of complex models given limited and noisy data. This leads to problems of parameter nonuniqueness and equifinality, which may negatively affect prediction uncertainties. A systematic way of controlling model complexity is therefore needed. We compare three model complexity control methods for hydrologic prediction, namely, cross validation (CV), Akaike's information criterion (AIC), and structural risk minimization (SRM). Results show that simulation of water flow using non-physically-based models (polynomials in this case) leads to increasingly better calibration fits as the model complexity (polynomial order) increases. However, prediction uncertainty worsens for complex non-physically-based models because of overfitting of noisy data. Incorporation of physically based constraints into the model (e.g., storage-discharge relationship) effectively bounds prediction uncertainty, even as the number of parameters increases. The conclusion is that overparameterization and equifinality do not lead to a continued increase in prediction uncertainty, as long as models are constrained by such physical principles. Complexity control of hydrologic models reduces parameter equifinality and identifies the simplest model that adequately explains the data, thereby providing a means of hydrologic generalization and classification. SRM is a promising technique for this purpose, as it (1) provides analytic upper bounds on prediction uncertainty, hence avoiding the computational burden of CV, and (2) extends the applicability of classic methods such as AIC to finite data. The main hurdle in applying SRM is the need for an a priori estimation of the complexity of the hydrologic model, as measured by its Vapnik-Chernovenkis (VC) dimension. Further research is needed in this area.
Lirette, Seth T; Aban, Inmaculada
For time-to-event outcomes in medical research, survival models are the most appropriate to use. Unlike logistic regression models, quantifying the predictive accuracy of these models is not a trivial task. We present the classes of concordance (C) statistics and R 2 statistics often used to assess the predictive ability of these models. The discussion focuses on Harrell's C, Kent and O'Quigley's R 2 , and Royston and Sauerbrei's R 2 . We present similarities and differences between the statistics, discuss the software options from the most widely used statistical analysis packages, and give a practical example using the Worcester Heart Attack Study dataset.
Yu. A. Litvinov
Full Text Available Ten different theoretical models are tested for their predictive power in the description of nuclear masses. Two sets of experimental masses are used for the test: the older set of 2003 and the newer one of 2011. The predictive power is studied in two regions of nuclei: the global region (Z, N ≥ 8 and the heavy-nuclei region (Z ≥ 82, N ≥ 126. No clear correlation is found between the predictive power of a model and the accuracy of its description of the masses.
Stock return predictability is subject to great uncertainty. In this paper we use the model confidence set approach to quantify uncertainty about expected utility from investment, accounting for potential return predictability. For monthly US data and six representative return prediction models, we...... find that confidence sets are very wide, change significantly with the predictor variables, and frequently include expected utilities for which the investor prefers not to invest. The latter motivates a robust investment strategy maximizing the minimal element of the confidence set. The robust investor...... allocates a much lower share of wealth to stocks compared to a standard investor....
Full Text Available Using mixed-species bird flocks as an example, we model the payoffs for two types of species from participating in multi-species animal groups. Salliers feed on mobile prey, are good sentinels and do not affect prey capture rates of gleaners; gleaners feed on prey on substrates and can enhance the prey capture rate of salliers by flushing prey, but are poor sentinels. These functional types are known from various animal taxa that form multi-species associations. We model costs and benefits of joining groups for a wide range of group compositions under varying abundances of two types of prey-prey on substrates and mobile prey. Our model predicts that gleaners and salliers show a conflict of interest in multi-species groups, because gleaners benefit from increasing numbers of salliers in the group, whereas salliers benefit from increasing gleaner numbers. The model also predicts that the limits to size and variability in composition of multi-species groups are driven by the relative abundance of different types of prey, independent of predation pressure. Our model emphasises resources as a primary driver of temporal and spatial group dynamics, rather than reproductive activity or predation per se, which have hitherto been thought to explain patterns of multi-species group formation and cohesion. The qualitative predictions of the model are supported by empirical patterns from both terrestrial and marine multi-species groups, suggesting that similar mechanisms might underlie group dynamics in a range of taxa. The model also makes novel predictions about group dynamics that can be tested using variation across space and time.
Full Text Available It is extremely important to predict the logistics requirements in a scientific and rational way. However, in recent years, the improvement effect on the prediction method is not very significant and the traditional statistical prediction method has the defects of low precision and poor interpretation of the prediction model, which cannot only guarantee the generalization ability of the prediction model theoretically, but also cannot explain the models effectively. Therefore, in combination with the theories of the spatial economics, industrial economics, and neo-classical economics, taking city of Zhuanghe as the research object, the study identifies the leading industry that can produce a large number of cargoes, and further predicts the static logistics generation of the Zhuanghe and hinterlands. By integrating various factors that can affect the regional logistics requirements, this study established a logistics requirements potential model from the aspect of spatial economic principles, and expanded the way of logistics requirements prediction from the single statistical principles to an new area of special and regional economics.
Beck, P. S.; Bohrer, G.; Wethington, S.; Bartlam-Brooks, H. L.; Powers, D. R.; Goetz, S. J.; Graham, C. H.
Animal migrations have evolved in response to spatio-temporal heterogeneity in resources, habitats, predation, and competition. Their reliance on disjunct habitats makes migratory animals potentially more vulnerable to extreme climate events or phenological changes at other trophic levels. The advent of affordable satellite-based tracking technology has revolutionized the study of animal movement in the past two decades. Understanding internal and external drivers of migratory behavior, and how they interact, is critical for migration ecology to move beyond solely the measurement and description of organism-level movement and to predict how environmental change might affect migrations. To achieve this, it is necessary to not only measure animals' movement but also their reliance on prevailing external, i.e. environmental, conditions prior to, and during migration. An increasingly wide array of satellite and model-derived gridded data sets that map environmental conditions at regular temporal intervals are now readily accessible because of standardized processing and data formats, as well as a variety of online portals that provide host data archives and/or on-demand processing free-of-charge. While they are often of coarser spatial resolution, these data can overcome many limitations of in situ measurements with regard to spatial extent and temporal frequency. We demonstrate the use of global gridded environmental time-series in the study of animal migrations through case studies. First we show how inter-annual weather variation in wintering habitats affects migratory behavior of broad-tailed hummingbirds and investigate how it carries over to their reproductive success and survival in summer habitats. To do so, we use vegetation indices as proxies of resource availability, and the NCEP Climate Forecast System Reanalysis (CFSR) to map known physiological constraints on the birds. Secondly, we investigated the effects of long as well as short-term variations in
Othman, A N; Mohd, W M N W; Noraini, S
The increasing population and expansion of settlements over hilly areas has greatly increased the impact of natural disasters such as landslide. Therefore, it is important to developed models which could accurately predict landslide hazard zones. Over the years, various techniques and models have been developed to predict landslide hazard zones. The aim of this paper is to access the accuracy of landslide prediction models developed by the authors. The methodology involved the selection of study area, data acquisition, data processing and model development and also data analysis. The development of these models are based on nine different landslide inducing parameters i.e. slope, land use, lithology, soil properties, geomorphology, flow accumulation, aspect, proximity to river and proximity to road. Rank sum, rating, pairwise comparison and AHP techniques are used to determine the weights for each of the parameters used. Four (4) different models which consider different parameter combinations are developed by the authors. Results obtained are compared to landslide history and accuracies for Model 1, Model 2, Model 3 and Model 4 are 66.7, 66.7%, 60% and 22.9% respectively. From the results, rank sum, rating and pairwise comparison can be useful techniques to predict landslide hazard zones
Dijkstra, J; Kebreab, E; Mills, J A N; Pellikaan, W F; López, S; Bannink, A; France, J
Current feed evaluation systems for dairy cattle aim to match nutrient requirements with nutrient intake at pre-defined production levels. These systems were not developed to address, and are not suitable to predict, the responses to dietary changes in terms of production level and product composition, excretion of nutrients to the environment, and nutrition related disorders. The change from a requirement to a response system to meet the needs of various stakeholders requires prediction of the profile of absorbed nutrients and its subsequent utilisation for various purposes. This contribution examines the challenges to predicting the profile of nutrients available for absorption in dairy cattle and provides guidelines for further improved prediction with regard to animal production responses and environmental pollution.The profile of nutrients available for absorption comprises volatile fatty acids, long-chain fatty acids, amino acids and glucose. Thus the importance of processes in the reticulo-rumen is obvious. Much research into rumen fermentation is aimed at determination of substrate degradation rates. Quantitative knowledge on rates of passage of nutrients out of the rumen is rather limited compared with that on degradation rates, and thus should be an important theme in future research. Current systems largely ignore microbial metabolic variation, and extant mechanistic models of rumen fermentation give only limited attention to explicit representation of microbial metabolic activity. Recent molecular techniques indicate that knowledge on the presence and activity of various microbial species is far from complete. Such techniques may give a wealth of information, but to include such findings in systems predicting the nutrient profile requires close collaboration between molecular scientists and mathematical modellers on interpreting and evaluating quantitative data. Protozoal metabolism is of particular interest here given the paucity of quantitative data
Breed, Greg A; Golson, Emily A.; Tinker, M. Tim
The home-range concept is central in animal ecology and behavior, and numerous mechanistic models have been developed to understand home range formation and maintenance. These mechanistic models usually assume a single, contiguous home range. Here we describe and implement a simple home-range model that can accommodate multiple home-range centers, form complex shapes, allow discontinuities in use patterns, and infer how external and internal variables affect movement and use patterns. The model assumes individuals associate with two or more home-range centers and move among them with some estimable probability. Movement in and around home-range centers is governed by a two-dimensional Ornstein-Uhlenbeck process, while transitions between centers are modeled as a stochastic state-switching process. We augmented this base model by introducing environmental and demographic covariates that modify transition probabilities between home-range centers and can be estimated to provide insight into the movement process. We demonstrate the model using telemetry data from sea otters (Enhydra lutris) in California. The model was fit using a Bayesian Markov Chain Monte Carlo method, which estimated transition probabilities, as well as unique Ornstein-Uhlenbeck diffusion and centralizing tendency parameters. Estimated parameters could then be used to simulate movement and space use that was virtually indistinguishable from real data. We used Deviance Information Criterion (DIC) scores to assess model fit and determined that both wind and reproductive status were predictive of transitions between home-range centers. Females were less likely to move between home-range centers on windy days, less likely to move between centers when tending pups, and much more likely to move between centers just after weaning a pup. These tendencies are predicted by theoretical movement rules but were not previously known and show that our model can extract meaningful behavioral insight from complex
Kim, Yeon-Jeong; Yeo, Sang-Gu; Park, Jae-Hak; Ko, Hyun-Jeong
Shigella was first discovered in 1897 and is a major causative agent of dysenteric diarrhea. The number of affected patients has decreased globally because of improved sanitary conditions; however, Shigella still causes serious problems in many subjects, including young children and the elderly, especially in developing countries. Although antibiotics may be effective, a vaccine would be the most powerful solution to combat shigellosis because of the emergence of drug-resistant strains. However, the development of a vaccine is hampered by several problems. First, there is no suitable animal model that can replace human-based studies for the investigation of the in vivo mechanisms of Shigella vaccines. Mouse, guinea pig, rat, rabbit, and nonhuman primates could be used as models for shigellosis, but they do not represent human shigellosis and each has its own weaknesses. However, a recent murine model based on peritoneal infection with virulent S. flexneri 2a is promising. Moreover, although the inflammatory responses and mechanisms such as pathogenassociated molecular patterns and danger-associated molecular patterns have been studied, the pathology and immunology of Shigella are still not clearly defined. Despite these obstacles, many vaccine candidates have been developed, including live attenuated, killed whole cells, conjugated, and subunit vaccines. The development of Shigella vaccines also demands considerations of the cost, routes of administration, ease of storage (stability), cross-reactivity, safety, and immunogenicity. The main aim of this review is to provide a detailed introduction to the many promising vaccine candidates and animal models currently available, including the newly developed mouse model.
Full Text Available The selection of an experimental animal model is of great importance in the study of bacterial virulence factors. Here, a bath infection of zebrafish larvae is proposed as an alternative model to study the virulence factors of A. hydrophila. Intraperitoneal infections in mice and trout were compared with bath infections in zebrafish larvae using specific mutants. The great advantage of this model is that bath immersion mimics the natural route of infection, and injury to the tail also provides a natural portal of entry for the bacteria. The implication of T3SS in the virulence of A. hydrophila was analysed using the AH-1::aopB mutant. This mutant was less virulent than the wild-type strain when inoculated into zebrafish larvae, as described in other vertebrates. However, the zebrafish model exhibited slight differences in mortality kinetics only observed using invertebrate models. Infections using the mutant AH-1∆vapA lacking the gene coding for the surface S-layer suggested that this protein was not totally necessary to the bacteria once it was inside the host, but it contributed to the inflammatory response. Only when healthy zebrafish larvae were infected did the mutant produce less mortality than the wild type. Variations between models were evidenced using the AH-1∆rmlB, which lacks the O-antigen lipopolysaccharide (LPS, and the AH-1∆wahD, which lacks the O-antigen LPS and part of the LPS outer-core. Both mutants showed decreased mortality in all of the animal models, but the differences between them were only observed in injured zebrafish larvae, suggesting that residues from the LPS outer core must be important for virulence. The greatest differences were observed using the AH-1ΔFlaB-J (lacking polar flagella and unable to swim and the AH-1::motX (non-motile but producing flagella. They were as pathogenic as the wild-type strain when injected into mice and trout, but no mortalities were registered in zebrafish larvae. This study
Xu, Ziyue; Mansoor, Awais; Mollura, Daniel J. [Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892 (United States); Bagci, Ulas, E-mail: firstname.lastname@example.org [Center for Research in Computer Vision (CRCV), University of Central Florida (UCF), Orlando, Florida 32816 (United States); Kramer-Marek, Gabriela [The Institute of Cancer Research, London SW7 3RP (United Kingdom); Luna, Brian [Microfluidic Laboratory Automation, University of California-Irvine, Irvine, California 92697-2715 (United States); Kubler, Andre [Department of Medicine, Imperial College London, London SW7 2AZ (United Kingdom); Dey, Bappaditya; Jain, Sanjay [Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 (United States); Foster, Brent [Department of Biomedical Engineering, University of California-Davis, Davis, California 95817 (United States); Papadakis, Georgios Z. [Radiology and Imaging Sciences, National Institutes of Health (NIH), Bethesda, Maryland 32892 (United States); Camp, Jeremy V. [Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202 (United States); Jonsson, Colleen B. [National Institute for Mathematical and Biological Synthesis, University of Tennessee, Knoxville, Tennessee 37996 (United States); Bishai, William R. [Howard Hughes Medical Institute, Chevy Chase, Maryland 20815 and Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231 (United States); Udupa, Jayaram K. [Medical Image Processing Group, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States)
Purpose: To develop an automated pulmonary image analysis framework for infectious lung diseases in small animal models. Methods: The authors describe a novel pathological lung and airway segmentation method for small animals. The proposed framework includes identification of abnormal imaging patterns pertaining to infectious lung diseases. First, the authors’ system estimates an expected lung volume by utilizing a regression function between total lung capacity and approximated rib cage volume. A significant difference between the expected lung volume and the initial lung segmentation indicates the presence of severe pathology, and invokes a machine learning based abnormal imaging pattern detection system next. The final stage of the proposed framework is the automatic extraction of airway tree for which new affinity relationships within the fuzzy connectedness image segmentation framework are proposed by combining Hessian and gray-scale morphological reconstruction filters. Results: 133 CT scans were collected from four different studies encompassing a wide spectrum of pulmonary abnormalities pertaining to two commonly used small animal models (ferret and rabbit). Sensitivity and specificity were greater than 90% for pathological lung segmentation (average dice similarity coefficient > 0.9). While qualitative visual assessments of airway tree extraction were performed by the participating expert radiologists, for quantitative evaluation the authors validated the proposed airway extraction method by using publicly available EXACT’09 data set. Conclusions: The authors developed a comprehensive computer-aided pulmonary image analysis framework for preclinical research applications. The proposed framework consists of automatic pathological lung segmentation and accurate airway tree extraction. The framework has high sensitivity and specificity; therefore, it can contribute advances in preclinical research in pulmonary diseases.
Full Text Available BACKGROUND: Modeling plays a critical role in mitigating impacts of seasonal influenza epidemics. Complex simulation models are currently at the forefront of evaluating optimal mitigation strategies at multiple scales and levels of organization. Given their evaluative role, these models remain limited in their ability to predict and forecast future epidemics leading some researchers and public-health practitioners to question their usefulness. The objective of this study is to evaluate the predictive ability of an existing complex simulation model of influenza spread. METHODS AND FINDINGS: We used extensive data on past epidemics to demonstrate the process of predictive validation. This involved generalizing an individual-based model for influenza spread and fitting it to laboratory-confirmed influenza infection data from a single observed epidemic (1998-1999. Next, we used the fitted model and modified two of its parameters based on data on real-world perturbations (vaccination coverage by age group and strain type. Simulating epidemics under these changes allowed us to estimate the deviation/error between the expected epidemic curve under perturbation and observed epidemics taking place from 1999 to 2006. Our model was able to forecast absolute intensity and epidemic peak week several weeks earlier with reasonable reliability and depended on the method of forecasting-static or dynamic. CONCLUSIONS: Good predictive ability of influenza epidemics is critical for implementing mitigation strategies in an effective and timely manner. Through the process of predictive validation applied to a current complex simulation model of influenza spread, we provided users of the model (e.g. public-health officials and policy-makers with quantitative metrics and practical recommendations on mitigating impacts of seasonal influenza epidemics. This methodology may be applied to other models of communicable infectious diseases to test and potentially improve
Hyder, Ayaz; Buckeridge, David L.; Leung, Brian
Background Modeling plays a critical role in mitigating impacts of seasonal influenza epidemics. Complex simulation models are currently at the forefront of evaluating optimal mitigation strategies at multiple scales and levels of organization. Given their evaluative role, these models remain limited in their ability to predict and forecast future epidemics leading some researchers and public-health practitioners to question their usefulness. The objective of this study is to evaluate the predictive ability of an existing complex simulation model of influenza spread. Methods and Findings We used extensive data on past epidemics to demonstrate the process of predictive validation. This involved generalizing an individual-based model for influenza spread and fitting it to laboratory-confirmed influenza infection data from a single observed epidemic (1998–1999). Next, we used the fitted model and modified two of its parameters based on data on real-world perturbations (vaccination coverage by age group and strain type). Simulating epidemics under these changes allowed us to estimate the deviation/error between the expected epidemic curve under perturbation and observed epidemics taking place from 1999 to 2006. Our model was able to forecast absolute intensity and epidemic peak week several weeks earlier with reasonable reliability and depended on the method of forecasting-static or dynamic. Conclusions Good predictive ability of influenza epidemics is critical for implementing mitigation strategies in an effective and timely manner. Through the process of predictive validation applied to a current complex simulation model of influenza spread, we provided users of the model (e.g. public-health officials and policy-makers) with quantitative metrics and practical recommendations on mitigating impacts of seasonal influenza epidemics. This methodology may be applied to other models of communicable infectious diseases to test and potentially improve their predictive
Sallam, Karim; Li, Yingxin; Sager, Philip T.; Houser, Steven R.; Wu, Joseph C.
Sudden Cardiac Death (SCD) is a common cause of death in patients with structural heart disease, genetic mutations or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with SCD. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell derived Cardiomyocytes (iPSC-CMs) resemble, but are not identical, to adult human cardiomyocytes, and provide a new platform for studying arrhythmic disorders leading to SCD. A variety of platforms exist to phenotype cellular models including conventional and automated patch clamp, multi-electrode array, and computational modeling. iPSC-CMs have been used to study Long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy and other hereditary cardiac disorders. Although iPSC-CMs are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of SCD. PMID:26044252
Svojanovská, Markéta; Stuchlík, Aleš
Roč. 4, č. 1 (2015), s. 3-18 ISSN 1805-7225 R&D Projects: GA MZd(CZ) NT13386 Institutional support: RVO:67985823 Keywords : schizophrenia * animal models * pharmacological models * genetic models * neurodevelopmental models * preclinical studies Subject RIV: FH - Neurology
Zanda, Mary Tresa; Fattore, Liana
Synthetic cannabinoids have long been studied for their therapeutic potentials. However, during the last decade, new generations of synthetic cannabinoid agonists appeared on the drug market. These new psychoactive substances are currently sold as 'marijuana-like' products as they claim to mimic the effects of the psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC). Yet, their effects are more intense and potent than THC, typically last longer and are often associated to serious psychiatric consequences. Animal models of drug addiction are frequently used in preclinical research to assess the abuse potential of new compounds, evaluate drug positive reinforcing effects and analyze drug-induced behaviors. Some of these protocols have been used recently to study the newly synthesized cannabinoid agonists and have started elucidating their pharmacology and actions in the brain. The aim of this review is to summarize the major findings reported by animal studies that tested synthetic cannabinoids of first, second, and third generation by using self-administration and reinstatement models, drug discrimination and conditioned place preference procedures. Altogether, behavioral studies clearly indicate that synthetic cannabinoids possess abuse liability, are likely to activate the brain reward circuit and induce positive subjective and reinforcing effects.
Antoniou, Efstathios; Margonis, Georgios Antonios; Angelou, Anastasios; Zografos, George C; Pikoulis, Emmanouil
It is well-known that inflammatory bowel disease (IBD) poses an increased, yet not definitely estimated, risk of colitis-associated colon cancer (CAC), which is considered a more aggressive and distinct in both genetic and molecular levels clinical entity compared to sporadic colorectal cancer (CRC). The present review discusses the cytokine networks involved in CAC-based translational findings from suitable animal models of the disease. Moreover, we summarize the most prominent data concerning the role of Th1, Th2, Th17 and anti-inflammatory cytokines in the pathogenesis of CAC. Last, we briefly address the controversies between basic science findings in IBD and CAC and suggest further directions regarding research on cytokines. This review should serve as a primer for clinicians and surgeons to understand the rapidly evolving field of cytokines in the context of CAC. The MEDLINE database was thoroughly searched using the keywords: cytokines, colitis-associated cancer, animal models, carcinogenesis. Additional articles were gathered and evaluated. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
This section is restricted to radiation-induced life shortening and cancer and mainly to studies with external radiation. The emphasis will be on the experimental data that are available and the experimental systems that could provide the type of data with which to either formulate or test models. Genetic effects which are of concern are not discussed in this section. Experimental animal radiation studies fall into those that establish general principles and those that demonstrate mechanisms. General principles include the influence of dose, radiation quality, dose rate, fractionation, protraction and such biological factors as age and gender. The influence of these factors are considered as general principles because they are independent, at least qualitatively, of the species studied. For example, if an increase in the LET of the radiation causes an increased effectiveness in cancer induction in a mouse a comparable increase in effectiveness can be expected in humans. Thus, models, whether empirical or mechanistic, formulated from experimental animal data should be generally applicable
Jordan, Christopher P; Wu, Kyle; Costello, John P; Ishibashi, Nobuyuki; Krieger, Axel; Kane, Timothy D; Kim, Peter; Berul, Charles I
We developed a minimally invasive epicardial pacemaker implantation method for infants and congenital heart disease patients for whom a transvenous approach is contraindicated. The piglet is an ideal model for technical development. In 5 piglets we introduced a needle through subxiphoid approach under thoracoscopic guidance, inserting a wire into the pericardial space. Pacing leads were affixed to the left ventricular free wall and left atrial appendage. After verifying functionality with atrial and ventricular pacing and sensing, animals were euthanized. Pacemaker monitoring occurred daily for 4 days in the fifth animal. Through minimally invasive pericardial access, we directly visualized and fixated pacing leads to the left ventricle and left atrial appendage, successfully pacing atrium and ventricle. Epicardial structures were visualized. One piglet had contralateral pneumothorax, which resolved with needle decompression. No other adverse events occurred. Minimally invasive epicardial pacemaker implantation in an infant model is feasible and effective. This innovation may be of value for pacing and resynchronization in infants and congenital heart disease patients. Survival studies with permanent generator implantation are under way. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Full Text Available Alzheimer’s disease (AD is the most common form of dementia, and the pathological changes of senile plaques (SPs and neurofibrillary tangles (NFTs in AD brains are well described. Clinically, a diagnosis remains a postmortem one, hampering both accurate and early diagnosis as well as research into potential new treatments. Visual deficits have long been noted in AD patients, and it is becoming increasingly apparent that histopathological changes already noted in the brain also occur in an extension of the brain; the retina. Due to the optically transparent nature of the eye, it is possible to image the retina at a cellular level noninvasively and thus potentially allow an earlier diagnosis as well as a way of monitoring progression and treatment effects. Transgenic animal models expressing amyloid precursor protein (APP presenilin (PS and tau mutations have been used successfully to recapitulate the pathological findings of AD in the brain. This paper will cover the ocular abnormalities that have been detected in these transgenic AD animal models.
This section is restricted to radiation-induced life shortening and cancer and mainly to studies with external radiation. The emphasis will be on the experimental data that are available and the experimental systems that could provide the type of data with which to either formulate or test models. Genetic effects which are of concern are not discussed in this section. Experimental animal radiation studies fall into those that establish general principles and those that demonstrate mechanisms. General principles include the influence of dose, radiation quality, dose rate, fractionation, protraction and such biological factors as age and gender. The influence of these factors are considered as general principles because they are independent, at least qualitatively, of the species studied. For example, if an increase in the LET of the radiation causes an increased effectiveness in cancer induction in a mouse a comparable increase in effectiveness can be expected in humans. Thus, models, whether empirical or mechanistic, formulated from experimental animal data should be generally applicable.
Full Text Available In skeletal muscle, dystroglycan (DG is the central component of the dystrophin-glycoprotein complex (DGC, a multimeric protein complex that ensures a strong mechanical link between the extracellular matrix and the cytoskeleton. Several muscular dystrophies arise from mutations hitting most of the components of the DGC. Mutations within the DG gene (DAG1 have been recently associated with two forms of muscular dystrophy, one displaying a milder and one a more severe phenotype. This review focuses specifically on the animal (murine and others model systems that have been developed with the aim of directly engineering DAG1 in order to study the DG function in skeletal muscle as well as in other tissues. In the last years, conditional animal models overcoming the embryonic lethality of the DG knock-out in mouse have been generated and helped clarifying the crucial role of DG in skeletal muscle, while an increasing number of studies on knock-in mice are aimed at understanding the contribution of single amino acids to the stability of DG and to the possible development of muscular dystrophy.
Ahmari, Susanne E.; Dougherty, Darin D.
Obsessive Compulsive Disorder (OCD) is a chronic, severe mental illness with up to 2–3% prevalence worldwide, which has been classified as one of the world’s 10 leading causes of illness-related disability according to the World Health Organization, largely because of the chronic nature of disabling symptoms 1. Despite the severity and high prevalence of this chronic and disabling disorder, there is still relatively limited understanding of its pathophysiology. However, this is now rapidly changing due to development of powerful technologies that can be used to dissect the neural circuits underlying pathologic behaviors. In this article, we describe recent technical advances that have allowed neuroscientists to start identifying the circuits underlying complex repetitive behaviors using animal model systems. In addition, we review current surgical and stimulation-based treatments for OCD that target circuit dysfunction. Finally, we discuss how findings from animal models may be applied in the clinical arena to help inform and refine targeted brain stimulation-based treatment approaches. PMID:25952989
Full Text Available Spinal cord injuries (SCI result in the loss of movement and sensory feedback as well as organs dysfunctions. For example, nearly all SCI subjects loose their bladder control and are prone to kidney failure if they do not proceed to intermittent (self- catheterization. Electrical stimulation of the sacral spinal roots with an implantable neuroprosthesis is a promising approach, with commercialized products, to restore continence and control micturition. However, many persons do not ask for this intervention since a surgical deafferentation is needed and the loss of sensory functions and reflexes become serious side effects of this procedure. Recent results renewed interest in spinal cord stimulation. Stimulation of existing pre-cabled neural networks involved in physiological processes regulation is suspected to enable synergic recruitment of spinal fibers. The development of direct spinal stimulation strategies aiming at bladder and bowel functions restoration would therefore appear as a credible alternative to existent solutions. However, a lack of suitable large animal model complicates these kinds of studies. In this article, we propose a new animal model of spinal stimulation -pig- and will briefly introduce results from one first acute experimental validation session.
Maizato, Marina J S; Taniguchi, Fabio P; Ambar, Rafael F; Pitombo, Ronaldo N M; Leirner, Adolfo A; Cestari, Idágene A; Stolf, Noedir A G
Glutaraldehyde is used in order to improve the mechanical and immunogenic properties of biological tissues, such as bovine pericardium membranes, used to manufacture heart valve bioprostheses. Lyophilization, also known as freeze-drying, preserves biological material without damage by freezing the water content and removing ice by sublimation. Through this process, dehydrated products of high quality may be obtained; also, the material may be easily handled. The lyophilization process reduces aldehyde residues in biological tissue previously treated with glutaraldehyde, thus promoting reduction of cytotoxicity, increasing resistance to inflammation, and possibly decreasing the potential for tissue calcification. The objective of this study was to chronically evaluate the calcification of bovine pericardium heart valve prostheses, previously lyophilized or not, in an animal model. Six-month-old sheep received implants of lyophilized and unlyophilized heart valve prostheses in the pulmonary position with right bypass. The study followed 16 animals for a period of 90 days. Right ventricle-pulmonary artery (RV/PA) transvalvular pressure gradient was evaluated before and immediately after implantation and before explantation, as were tissue calcium, inflammation intensity, and thrombosis and pannus formation. The t-test was used for statistical analysis. Twelve animals survived to the end of the experiment, but one of the animals in the control group had endocarditis and was excluded from the data. Four animals died early. The mean RV/PA gradient on implantation was 2.0 ± 1.6 mm Hg in the control group and 6.2 ± 4.1 mm Hg in the lyophilized group (P = 0.064). This mean gradient increased at explantation to 7.7 ± 3.9 mm Hg and 8.6 ± 5.8 mm Hg, respectively (P = 0.777). The average calcium content in the tissue leaflets after 3 months was 21.6 ± 39.1 mg Ca(2+)/g dry weight in the control group, compared with an average content of 41.2 ± 46.9 mg Ca(2+)/g dry weight
Full Text Available Parkinson's disease (PD is a common progressive neurodegenerative disorder. The major pathological hallmarks of PD are the selective loss of nigrostriatal dopaminergic neurons and the presence of intraneuronal aggregates termed Lewy bodies (LBs, but the pathophysiological mechanisms are not fully understood. Epidemiologically, environmental neurotoxins such as pesticides are promising candidates for causative factors of PD. Oxidative stress and mitochondrial dysfunction induced by these toxins could contribute to the progression of PD. While most cases of PD are sporadic, specific mutations in genes that cause familial forms of PD have led to provide new insights into its pathogenesis. This paper focuses on animal models of both toxin-induced and genetically determined PD that have provided significant insight for understanding this disease. We also discuss the validity, benefits, and limitations of representative models.
Full Text Available This article is a summary about the current research of nicotine effects on the nervous system and its relationship to the generation of an addictive behavior. Like other drugs of abuse, nicotine activates the reward pathway, which in turn is involved in certain psychiatric diseases. There are individuals who have a high vulnerability to nicotine addiction. This may be due to genetic and epigenetic factors and/or the environment. In this review, we described some epigenetic factors that may be involved in those phenomena. The two animal models most widely used for studying the reinforcing effects of nicotine are: self-administration and conditioning place preference (CPP. Here, we emphasized the CPP, due to its potential application in humans. In addition, we described the locomotor activity model (as a measure of psychostimulant effects to study vulnerability to drugs of abuse
Monteiro, Patricia; Feng, Guoping
Obsessive-Compulsive Disorder (OCD) affects 2–3% of the worldwide population and can cause significant distress and disability to its sufferers. Substantial challenges remain in the field of OCD research and therapeutics. Approved interventions only partially alleviate symptoms, with 30–40% of patients being resistant to treatment. Research evidence points towards the involvement of cortico-striato-thalamocortical circuitry (CSTC) although OCD’s etiology is still unknown. This review will focus on the most recent behavior, genetics and neurophysiological findings from animal models of OCD. Based on evidence from these models and parallels with human studies, we discuss the circuit hyperactivity hypothesis for OCD, a potential circuitry dysfunction of action termination, and the involvement of candidate genes. Adding a more biologically-valid framework to OCD will help us define and test new hypotheses and facilitate the development of targeted therapies based on disease-specific mechanisms. PMID:26037910
Nguyen, Cattram D; Lee, Katherine J; Carlin, John B
Multiple imputation is gaining popularity as a strategy for handling missing data, but there is a scarcity of tools for checking imputation models, a critical step in model fitting. Posterior predictive checking (PPC) has been recommended as an imputation diagnostic. PPC involves simulating "replicated" data from the posterior predictive distribution of the model under scrutiny. Model fit is assessed by examining whether the analysis from the observed data appears typical of results obtained from the replicates produced by the model. A proposed diagnostic measure is the posterior predictive "p-value", an extreme value of which (i.e., a value close to 0 or 1) suggests a misfit between the model and the data. The aim of this study was to evaluate the performance of the posterior predictive p-value as an imputation diagnostic. Using simulation methods, we deliberately misspecified imputation models to determine whether posterior predictive p-values were effective in identifying these problems. When estimating the regression parameter of interest, we found that more extreme p-values were associated with poorer imputation model performance, although the results highlighted that traditional thresholds for classical p-values do not apply in this context. A shortcoming of the PPC method was its reduced ability to detect misspecified models with increasing amounts of missing data. Despite the limitations of posterior predictive p-values, they appear to have a valuable place in the imputer's toolkit. In addition to automated checking using p-values, we recommend imputers perform graphical checks and examine other summaries of the test quantity distribution. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Tuikka, A.I., E-mail: email@example.com [University of Eastern Finland, Department of Environmental and Biological Sciences, P.O. Box 111, FI-80101 Joensuu (Finland); Leppänen, M.T., E-mail: Matti.T.Leppanen@ymparisto.fi [Finnish Environment Institute, Laboratories/Research and Innovation Laboratory, P.O. Box 35, University of Jyväskylä, FI-40014 Jyväskylä (Finland); Akkanen, J., E-mail: firstname.lastname@example.org [University of Eastern Finland, Department of Environmental and Biological Sciences, P.O. Box 111, FI-80101 Joensuu (Finland); Sormunen, A.J., E-mail: Arto.Sormunen@mamk.fi [University of Eastern Finland, Department of Environmental and Biological Sciences, P.O. Box 111, FI-80101 Joensuu (Finland); Leonards, P.E.G., E-mail: email@example.com [Institute for Environmental Studies, Vrije Universiteit Amsterdam, De Boelelaan 1087, 1081 HV Amsterdam (Netherlands); Hattum, B. van, E-mail: firstname.lastname@example.org [Institute for Environmental Studies, Vrije Universiteit Amsterdam, De Boelelaan 1087, 1081 HV Amsterdam (Netherlands); Vliet, L.A. van, E-mail: email@example.com [Ministry of Transport, Public Works and Water Management, National Institute for Coastal and Marine Management/RIKZ, P.O. Box 207, 9750 AE Haren (Netherlands); Brack, W., E-mail: firstname.lastname@example.org [Helmholtz Centre for Environmental Research - UFZ, Department of Effect-Directed Analysis, Permoserstraße 15, 04318 Leipzig (Germany); Smedes, F., E-mail: email@example.com [Ministry of Transport, Public Works and Water Management, National Institute for Coastal and Marine Management/RIKZ, P.O. Box 207, 9750 AE Haren (Netherlands); and others
There were two main objectives in this study. The first was to compare the accuracy of different prediction methods for the chemical concentrations of polyaromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in the organism, based on the measured chemical concentrations existing in sediment dry matter or pore water. The predicted tissue concentrations were compared to the measured ones after 28-day laboratory test using oligochaeta worms (Lumbriculus variegatus). The second objective was to compare the bioaccumulation of PAHs and PCBs in the laboratory test with the in situ bioaccumulation of these compounds. Using the traditional organic carbon-water partitioning model, tissue concentrations were greatly overestimated, based on the concentrations in the sediment dry matter. Use of an additional correction factor for black carbon with a two-carbon model, significantly improved the bioaccumulation predictions, thus confirming that black carbon was important in binding the chemicals and reducing their accumulation. The predicted PAH tissue concentrations were, however, high compared to the observed values. The chemical concentrations were most accurately predicted from their freely dissolved pore water concentrations, determined using equilibrium passive sampling. The patterns of PCB and PAH accumulation in sediments for laboratory-exposed L. variegatus were similar to those in field-collected Lumbriculidae worms. Field-collected benthic invertebrates and L. variegatus accumulated less PAHs than PCBs with similar lipophilicity. The biota to sediment accumulation factors of PAHs tended to decrease with increasing sediment organic carbon normalized concentrations. The presented data yields bioconcentration factors (BCF) describing the chemical water-lipid partition, which were found to be higher than the octanol-water partition coefficients, but on a similar level with BCFs drawn from relevant literature. In conclusion, using the two-carbon model method
Fischer, Paul; Larsen, Simon; Thomsen, Claus
we are considering here, is to predict the secondary structure from the primary one. To this end we train a Markov model on training data and then use it to classify parts of unknown protein sequences as sheets, helices or coils. We show how to exploit the directional information contained...... in the Markov model for this task. Classifications that are purely based on statistical models might not always be biologically meaningful. We present combinatorial methods to incorporate biological background knowledge to enhance the prediction performance....
In order to reach robust and simplified yet accurate prediction models, energy based principle are commonly used in many fields of acoustics, especially in building acoustics. This includes simple energy flow models, the framework of statistical energy analysis (SEA) as well as more elaborated...... principles as, e.g., wave intensity analysis (WIA). The European standards for building acoustic predictions, the EN 12354 series, are based on energy flow and SEA principles. In the present paper, different energy based prediction models are discussed and critically reviewed. Special attention is placed...... on underlying basic assumptions, such as diffuse fields, high modal overlap, resonant field being dominant, etc., and the consequences of these in terms of limitations in the theory and in the practical use of the models....
Full Text Available Early indication of bancruptcy is important for a company. If companies aware of potency of their bancruptcy, they can take a preventive action to anticipate the bancruptcy. In order to detect the potency of a bancruptcy, a company can utilize a a model of bancruptcy prediction. The prediction model can be built using a machine learning methods. However, the choice of machine learning methods should be performed carefully. Because the suitability of a model depends on the problem specifically. Therefore, in this paper we perform a comparative study of several machine leaning methods for bancruptcy prediction. According to the comparative study, the performance of several models that based on machine learning methods (k-NN, fuzzy k-NN, SVM, Bagging Nearest Neighbour SVM, Multilayer Perceptron(MLP, Hybrid of MLP + Multiple Linear Regression, it can be showed that fuzzy k-NN method achieve the best performance with accuracy 77.5%
Woods, H Arthur; Smith, Jennifer N
For terrestrial animals and plants, a fundamental cost of living is water vapor lost to the atmosphere during exchange of metabolic gases. Here, by bringing together previously developed models for specific taxa, we integrate properties common to all terrestrial gas exchangers into a universal model of water loss. The model predicts that water loss scales to gas exchange with an exponent of 1 and that the amount of water lost per unit of gas exchanged depends on several factors: the surface temperature of the respiratory system near the outside of the organism, the gas consumed (oxygen or carbon dioxide), the steepness of the gradients for gas and vapor, and the transport mode (convective or diffusive). Model predictions were largely confirmed by data on 202 species in five taxa--insects, birds, bird eggs, mammals, and plants--spanning nine orders of magnitude in rate of gas exchange. Discrepancies between model predictions and data seemed to arise from biologically interesting violations of model assumptions, which emphasizes how poorly we understand gas exchange in some taxa. The universal model provides a unified conceptual framework for analyzing exchange-associated water losses across taxa with radically different metabolic and exchange systems.
Aman, Saima; Frincu, Marc; Chelmis, Charalampos; Noor, Muhammad; Simmhan, Yogesh; Prasanna, Viktor K.
As Smart Grids move closer to dynamic curtailment programs, Demand Response (DR) events will become necessary not only on fixed time intervals and weekdays predetermined by static policies, but also during changing decision periods and weekends to react to real-time demand signals. Unique challenges arise in this context vis-a-vis demand prediction and curtailment estimation and the transformation of such tasks into an automated, efficient dynamic demand response (D2R) process. While existing work has concentrated on increasing the accuracy of prediction models for DR, there is a lack of studies for prediction models for D2R, which we address in this paper. Our first contribution is the formal definition of D2R, and the description of its challenges and requirements. Our second contribution is a feasibility analysis of very-short-term prediction of electricity consumption for D2R over a diverse, large-scale dataset that includes both small residential customers and large buildings. Our third, and major contribution is a set of insights into the predictability of electricity consumption in the context of D2R. Specifically, we focus on prediction models that can operate at a very small data granularity (here 15-min intervals), for both weekdays and weekends - all conditions that characterize scenarios for D2R. We find that short-term time series and simple averaging models used by Independent Service Operators and utilities achieve superior prediction accuracy. We also observe that workdays are more predictable than weekends and holiday. Also, smaller customers have large variation in consumption and are less predictable than larger buildings. Key implications of our findings are that better models are required for small customers and for non-workdays, both of which are critical for D2R. Also, prediction models require just few days’ worth of data indicating that small amounts of
Freitas, F F B P; Fernandes, H B; Piauilino, C A; Pereira, S S; Carvalho, K I M; Chaves, M H; Soares, P M G; Miura, L M C V; Leite, J R S A; Oliveira, R C M; Oliveira, F A
The stem barks of Zanthoxylum rhoifolium Lam. (Rutaceae), locally known as "mamica de cadela", are popularly used in dyspepsies, stomachic, tonic, antitumoral, antipyretic and are used in treating flatulence and colic. The objective of this study was to evaluate the gastroprotective effect of the ethanolic extract of Zanthoxylum rhoifolium (EEZR) stem barks in acute gastric lesion models, investigating their possible mechanisms. Mice were used for the evaluation of the acute toxicity, and mice and rats to study the gastroprotective activity. The gastroprotective action of EEZR was analyzed in the absolute ethanol, HCl/ethanol and indomethacin-induced gastric lesion models in mice, hypothermic-restraint stress, and ischemia/reperfusion in rats. In the investigation of the gastroprotective mechanisms of EEZR, the participation of the NO-synthase pathway, ATP-sensitive potassium channels (K(ATP)), the levels of the non-protein sulfhydril groups (NP-SH) and the catalase activity using the ethanol-induced gastric mucosa lesion model and the quantification of the gastric mucus and the antisecretory activity through pylorus ligature model in rats were analyzed. The animals did not present any signs of acute toxicity for the EEZR (up to the 4 g/kg dose, po), and it was not possible to calculate the DL(50). EEZR (125-500 mg/kg) exhibited a significant gastroprotective effect in absolute ethanol, HCl/ethanol, hypothermic-restraint stress, and ischemia/reperfusion-induced gastric lesion models. EEZR (250 and 500 mg/kg) exhibited still a gastroprotective activity in the indomethacin-induced ulcer model. Gastroprotection of EEZR was significantly decreased in pre-treated mice with l-NAME or glibenclamide, the respective nitric oxide synthase and K(ATP) channels inhibitors. Our studies revealed that EEZR (500 mg/kg) prevented the decrease of the non-protein sulfhydril groups (NP-SH) and increased the catalase levels in ethanol-treated animals. Furthermore, the extract (500 mg
The model quality assessment problem consists in the a priori estimation of the overall and per-residue accuracy of protein structure predictions. Over the past years, a number of methods have been developed to address this issue and CASP established a prediction category to evaluate their performance in 2006. In 2008 the experiment was repeated and its results are reported here. Participants were invited to infer the correctness of the protein models submitted by the registered automatic servers. Estimates could apply to both whole models and individual amino acids. Groups involved in the tertiary structure prediction categories were also asked to assign local error estimates to each predicted residue in their own models and their results are also discussed here. The correlation between the predicted and observed correctness measures was the basis of the assessment of the results. We observe that consensus-based methods still perform significantly better than those accepting single models, similarly to what was concluded in the previous edition of the experiment. © 2009 WILEY-LISS, INC.
Lund, Thomas Bøker; Sørensen, Thorkild I.A.; Olsson, I. Anna S.
for the view that this form of animal use, unlike some other forms of animal-based medical research, cannot be defended. The first argument leans heavily on the notion that people themselves are responsible for developing obesity and so-called 'lifestyle' diseases; the second involves the claim that animal......Animal use in medical research is widely accepted on the basis that it may help to save human lives and improve their quality of life. Recently, however, objections have been made specifically to the use of animals in scientific investigation of human obesity. This paper discusses two arguments...... of animals in obesity research as especially problematic....
This study summarizes the design of a Model Predictive Controller (MPC) in Tüpraş, İzmit Refinery Hydrocracker Unit Reactors. Hydrocracking process, in which heavy vacuum gasoil is converted into lighter and valuable products at high temperature and pressure is described briefly. Controller design description, identification and modeling studies are examined and the model variables are presented. WABT (Weighted Average Bed Temperature) equalization and conversion increase are simulate...
Augustine, Alison Deckhut; Gondré-Lewis, Timothy; McBride, William; Miller, Lara; Pellmar, Terry C; Rockwell, Sara
Current events throughout the world underscore the growing threat of different forms of terrorism, including radiological or nuclear attack. Pharmaceutical products and other approaches are needed to protect the civilian population from radiation and to treat those with radiation-induced injuries. In the event of an attack, radiation exposures will be heterogeneous in terms of both dose and quality, depending on the type of device used and each victim's location relative to the radiation source. Therefore, methods are needed to protect against and treat a wide range of early and slowly developing radiation-induced injuries. Equally important is the development of rapid and accurate biodosimetry methods for estimating radiation doses to individuals and guiding clinical treatment decisions. Acute effects of high-dose radiation include hematopoietic cell loss, immune suppression, mucosal damage (gastrointestinal and oral), and potential injury to other sites such as the lung, kidney and central nervous system (CNS). Long-term effects, as a result of both high- and low-dose radiation, include dysfunction or fibrosis in a wide range of organs and tissues and cancer. The availability of appropriate types of animal models, as well as adequate numbers of animals, is likely to be a major bottleneck in the development of new or improved radioprotectors, mitigators and therapeutic agents to prevent or treat radiation injuries and of biodosimetry methods to measure radiation doses to individuals.
Risling, Mårten; Davidsson, Johan
A blast injury is a complex type of physical trauma resulting from the detonation of explosive compounds and has become an important issue due to the use of improvised explosive devices (IED) in current military conflicts. Blast-induced neurotrauma (BINT) is a major concern in contemporary military medicine and includes a variety of injuries that range from mild to lethal. Extreme forces and their complex propagation characterize BINT. Modern body protection and the development of armored military vehicles can be assumed to have changed the outcome of BINT. Primary blast injuries are caused by overpressure waves whereas secondary, tertiary, and quaternary blast injuries can have more varied origins such as the impact of fragments, abnormal movements, or heat. The characteristics of the blast wave can be assumed to be significantly different in open field detonations compared to explosions in a confined space, such an armored vehicle. Important parameters include peak pressure, duration, and shape of the pulse. Reflections from walls and armor can make the prediction of effects in individual cases very complex. Epidemiological data do not contain information of the comparative importance of the different blast mechanisms. It is therefore important to generate data in carefully designed animal models. Such models can be selective reproductions of a primary blast, penetrating injuries from fragments, acceleration movements, or combinations of such mechanisms. It is of crucial importance that the physical parameters of the employed models are well characterized so that the experiments can be reproduced in different laboratory settings. Ideally, pressure recordings should be calibrated by using the same equipment in several laboratories. With carefully designed models and thoroughly evaluated animal data it should be possible to achieve a translation of data between animal and clinical data. Imaging and computer simulation represent a possible link between experiments
Lewis, Russell E; Verweij, Paul E
Infections caused by triazole-resistant Aspergillus fumigatus are associated with a higher probability of treatment failure and mortality. Because clinical experience in managing these infections is still limited, mouse models of invasive aspergillosis fulfill a critical void for studying treatment regimens designed to overcome resistance. The type of immunosuppression, the route of infection, the timing of antifungal administration, and the end points used to assess antifungal activity affect the interpretation of data from these models. Nevertheless, these models provide important insights that help guide treatment decisions in patients with triazole-resistant invasive aspergillosis. Animal models confirmed that a high triazole minimal inhibitory concentration corresponded with triazole treatment failure and that the efficacy of other classes of drugs, such as the polyenes and echinocandins, was not affected by the presence of triazole resistance mutations. Furthermore, the feasibility of triazole dose escalation, combination therapy, and prophylaxis were explored as strategies to overcome resistance. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: firstname.lastname@example.org.
Full Text Available Xiang Li,1,2 Guangsheng Li,1,3 Keith Dip-Kei Luk,1 Yong Hu1–3 1Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong, 2Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, The University of Hong Kong-Shenzhen Hospital, Shenzhen, 3Spinal Division, Department of Orthopaedics, Affiliated Hospital of Guangdong Medical University, Guangdong, People’s Republic of China Background: Cervical spondylotic myelopathy (CSM is a chronic compression injury of the spinal cord, with potentially reversible conditions after surgical decompression, and a unique model of incomplete spinal cord injury. Several animal studies showed pathological changes of demyelination, axon loss and neuron apoptosis in rats with chronic spinal cord compression. However, there is a limited understanding of the neurological change in the spinal cord after surgical decompression. The aim of this study was to validate the neurorestoratology of myelopathic lesions in the spinal cord in a rat model. Materials and methods: A total of 16 adult Sprague-Dawley rats were divided into four groups: sham control (group 1; CSM model with 4-week chronic compression (group 2, 2 weeks (group 3 and 4 weeks (group 4 after surgical decompression of CSM model. The compression and decompression were verified by magnetic resonance imaging (MRI test. Neurological function was evaluated by Basso, Beattie, and Bresnahan (BBB locomotor rating scale, ladder rung walking test and somatosensory-evoked potentials (SEPs. Neuropathological change was evaluated by histological examinations. Results: MRI confirmed the compression of the cervical spinal cord as well as the reshaping of cord morphology after decompression. After decompression, significant changes of neurological function were observed in BBB scores (p < 0.01, F = 10.52, ladder rung walking test (p < 0.05, F = 14.21 and latencies (p < 0.05, F = 5.76 and amplitudes (p < 0.05, F = 3.8 of
Ohlemiller, Kevin K
Schuknecht proposed a discrete form of presbycusis in which hearing loss results principally from degeneration of cochlear stria vascularis and decline of the endocochlear potential (EP). This form was asserted to be genetically linked, and to arise independently from age-related pathology of either the organ of Corti or cochlear neurons. Although extensive strial degeneration in humans coincides with hearing loss, EPs have never been measured in humans, and age-related EP reduction has never been verified. No human genes that promote strial presbycusis have been identified, nor is its pathophysiology well understood. Effective application of animal models to this issue requires models demonstrating EP decline, and preferably, genetically distinct strains that vary in patterns of EP decline and its cellular correlates. Until recently, only two models, Mongolian gerbils and Tyrp1(B-lt) mice, were known to undergo age-associated EP reduction. Detailed studies of seven inbred mouse strains have now revealed three strains (C57BL/6J, B6.CAST-Cdh23(CAST), CBA/J) showing essentially no EP decline with age, and four strains ranging from modest to severe EP reduction (C57BL/6-Tyr(c-2J), BALB/cJ, CBA/CaJ, NOD.NON-H2(nbl)/LtJ). Collectively, animal models support five basic principles regarding a strial form of presbycusis: 1) Progressive EP decline from initially normal levels as a defining characteristic; 2) Non-universality, not all age-associated hearing loss involves EP decline; 3) A clear genetic basis; 4) Modulation by environment or stochastic events; and 5) Independent strial, organ of Corti, and neural pathology. Shared features between human strial presbycusis, gerbils, and BALB/cJ and C57BL/6-Tyr(c-2J) mice further suggest this condition frequently begins with strial marginal cell dysfunction and loss. By contrast, NOD.NON-H2(nbl) mice may model a sequence more closely associated with strial microvascular disease. Additional studies of these and other inbred mouse
Pinnapureddy, Ashish R; Stayner, Cherie; McEwan, John; Baddeley, Olivia; Forman, John; Eccles, Michael R
Animals that accurately model human disease are invaluable in medical research, allowing a critical understanding of disease mechanisms, and the opportunity to evaluate the effect of therapeutic compounds in pre-clinical studies. Many types of animal models are used world-wide, with the most common being small laboratory animals, such as mice. However, rodents often do not faithfully replicate human disease, despite their predominant use in research. This discordancy is due in part to physiological differences, such as body size and longevity. In contrast, large animal models, including sheep, provide an alternative to mice for biomedical research due to their greater physiological parallels with humans. Completion of the full genome sequences of many species, and the advent of Next Generation Sequencing (NGS) technologies, means it is now feasible to screen large populations of domesticated animals for genetic variants that resemble human genetic diseases, and generate models that more accurately model rare human pathologies. In this review, we discuss the notion of using sheep as large animal models, and their advantages in modelling human genetic disease. We exemplify several existing naturally occurring ovine variants in genes that are orthologous to human disease genes, such as the Cln6 sheep model for Batten disease. These, and other sheep models, have contributed significantly to our understanding of the relevant human disease process, in addition to providing opportunities to trial new therapies in animals with similar body and organ size to humans. Therefore sheep are a significant species with respect to the modelling of rare genetic human disease, which we summarize in this review.
Full Text Available Animal welfare organizations typically take in cats with unknown levels of socialization towards humans, ranging from unsocialized cats well-socialized but lost pets. Agencies typically determine the socialization status and disposition options of cats within three days, when even a well-socialized pet may be too frightened of the unfamiliar surroundings to display its typical behavior. This is the third part of a three-phase project to develop and evaluate a reliable and valid tool to predict cats’ socialization levels. We recruited cats from the full spectrum of socialization and, using information from the cats’ caregivers regarding typical behavior toward familiar and unfamiliar people, assigned each cat to a Socialization Category. This information was compared to the cats’ behavior during three days of structured assessments conducted in a shelter-like setting. The results of logistic regression modeling generated two models using assessments from the mornings of the second and third day, focusing on predicting shyer or more aloof but socialized cats. Using the coefficients from each of these models, two sets of points were calculated which were useful in differentiating More and Less Socialized cats. In combination with key socialized behaviors, these points were able to fairly accurately identify More and Less Socialized cats.
Bailey, Joseph D; Wallis, Jamie; Codling, Edward A
Understanding how an individual animal is able to navigate through its environment is a key question in movement ecology that can give insight into observed movement patterns and the mechanisms behind them. Efficiency of navigation is important for behavioral processes at a range of different spatio-temporal scales, including foraging and migration. Random walk models provide a standard framework for modeling individual animal movement and navigation. Here we consider a vector-weighted biased and correlated random walk (BCRW) model for directed movement (taxis), where external navigation cues are balanced with forward persistence. We derive a mathematical approximation of the expected navigational efficiency for any BCRW of this form and confirm the model predictions using simulations. We demonstrate how the navigational efficiency is related to the weighting given to forward persistence and external navigation cues, and highlight the counter-intuitive result that for low (but realistic) levels of error on forward persistence, a higher navigational efficiency is achieved by giving more weighting to this indirect navigation cue rather than direct navigational cues. We discuss and interpret the relevance of these results for understanding animal movement and navigation strategies. © 2017 by the Ecological Society of America.
Animal studies are usually to predict the value of new compounds and to assess their incorporation into schemes to reduce or clarify recognized hazards. There are two assumptions, that animal models are appropriate and dose-response relationship can be derived. Such tests cannot provide definite evidence about the safety of such medical agents in man. Examples are given of data arising from studies of progestogens or oestrogens in animals in relation to clinical conditions. The scientific quality of these tests depends on the adequacy of an appropriate design, competent staff and a correct evaluation of the results.
Koerner, Stephan; Holzaepfel, Frank; Ahmad, Nash'at N.
Several multi-model ensemble methods are investigated for predicting wake vortex transport and decay. This study is a joint effort between National Aeronautics and Space Administration and Deutsches Zentrum fuer Luft- und Raumfahrt to develop a multi-model ensemble capability using their wake models. An overview of different multi-model ensemble methods and their feasibility for wake applications is presented. The methods include Reliability Ensemble Averaging, Bayesian Model Averaging, and Monte Carlo Simulations. The methodologies are evaluated using data from wake vortex field experiments.
Picher-Martel, Vincent; Valdmanis, Paul N; Gould, Peter V; Julien, Jean-Pierre; Dupré, Nicolas
Amyotrophic Lateral Sclerosis (ALS) is the most frequent motor neuron disease in adults. Classical ALS is characterized by the death of upper and lower motor neurons leading to progressive paralysis. Approximately 10 % of ALS patients have familial form of the disease. Numerous different gene mutations have been found in familial cases of ALS, such as mutations in superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43), fused in sarcoma (FUS), C9ORF72, ubiquilin-2 (UBQLN2), optineurin (OPTN) and others. Multiple animal models were generated to mimic the disease and to test future treatments. However, no animal model fully replicates the spectrum of phenotypes in the human disease and it is difficult to assess how a therapeutic effect in disease models can predict efficacy in humans. Importantly, the genetic and phenotypic heterogeneity of ALS leads to a variety of responses to similar treatment regimens. From this has emerged the concept of personalized medicine (PM), which is a medical scheme that combines study of genetic, environmental and clinical diagnostic testing, including biomarkers, to individualized patient care. In this perspective, we used subgroups of specific ALS-linked gene mutations to go through existing animal models and to provide a comprehensive profile of the differences and similarities between animal models of disease and human disease. Finally, we reviewed application of biomarkers and gene therapies relevant in personalized medicine approach. For instance, this includes viral delivering of antisense oligonucleotide and small interfering RNA in SOD1, TDP-43 and C9orf72 mice models. Promising gene therapies raised possibilities for treating differently the major mutations in familial ALS cases.
Soga, Ryo; Shiramatsu, Tomoyo I; Kanzaki, Ryohei; Takahashi, Hirokazu
Biased or too strong preference for a particular object is often problematic, resulting in addiction and phobia. In animal models, alternative forced-choice tasks have been routinely used, but such preference test is far from daily situations that addicts or phobic are facing. In the present study, we developed a behavioral assay to evaluate the preference of sounds in rodents. In the assay, several sounds were presented according to the position of free-moving rats, and quantified the sound preference based on the behavior. A particular tone was paired with microstimulation to the ventral tegmental area (VTA), which plays central roles in reward processing, to increase sound preference. The behaviors of rats were logged during the classical conditioning for six days. Consequently, some behavioral indices suggest that rats search for the conditioned sound. Thus, our data demonstrated that quantitative evaluation of preference in the behavioral assay is feasible.
Fernández García, María Teresa; Núñez Martínez, Paula; García de la Fuente, Vanessa; Sánchez Pitiot, Marta; Muñiz Salgueiro, María Del Carmen; Perillán Méndez, Carmen; Argüelles Luis, Juan; Astudillo González, Aurora
The kidneys are vital organs responsible for excretion, fluid and electrolyte balance and hormone production. The nephrons are the kidney's functional and structural units. The number, size and distribution of the nephron components contain relevant information on renal function. Stereology is a branch of morphometry that applies mathematical principles to obtain three-dimensional information from serial, parallel and equidistant two-dimensional microscopic sections. Because of the complexity of stereological studies and the lack of scientific literature on the subject, the aim of this paper is to clearly explain, through animal models, the basic concepts of stereology and how to calculate the main kidney stereological parameters that can be applied in future experimental studies. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.
Taylor, G.N.; Gardner, P.A.; Jones, C.W.; Lloyd, R.D.; Mays, C.W.
Two small rodent species, the grasshopper mouse (Onychomys leucogaster) and the deer mouse (Peromyscus maniculatus) have tenacious retention in the liver and skeleton of plutonium and americium. The retention following intraperitoneal injection of Pu and Am in citrate solution ranged from 20 to 47% (liver) and 19 to 42% (skeleton), relatively independent of post-injection times, varying from 30 to 125 days. Based on observations extended to 125 days post-injection, the biological half-times appeared to be long. Both of these rodents are relatively long-lived (median lifespans of approximately 1400 days), breed well in captivity, and adapt suitably to laboratory conditions. It is suggested that these two species of mice, in which plutonium is partitioned between the skeleton and liver in a manner similar to that of man, may be useful animal models for actinide toxicity studies
Gavin, P.R.; Kraft, S.L.; DeHaan, C.E.; Moore, M.P.; Griebenow, M.L.
An epithermal neutron beam is needed to treat relatively deep seated tumors. The scattering characteristics of neutrons in this energy range dictate that in vivo experiments be conducted in a large animal to prevent unacceptable total body irradiation. The canine species has proven an excellent model to evaluate the various problems of boron neutron capture utilizing an epithermal neutron beam. This paper discusses three major components of the authors study: (1) the pharmacokinetics of borocaptate sodium (NA 2 B 12 H 11 SH or BSH) in dogs with spontaneously occurring brain tumors, (2) the radiation tolerance of normal tissues in the dog using an epithermal beam alone and in combination with borocaptate sodium, and (3) initial treatment of dogs with spontaneously occurring brain tumors utilizing borocaptate sodium and an epithermal neutron beam
Fetoni, Anna R; Picciotti, Pasqualina M; Paludetti, Gaetano; Troiani, Diana
Presbycusis is the most common cause of hearing loss in aged subjects, reducing individual's communicative skills. Age related hearing loss can be defined as a progressive, bilateral, symmetrical hearing loss due to age related degeneration and it can be considered a multifactorial complex disorder, with both environmental and genetic factors contributing to the aetiology of the disease. The decline in hearing sensitivity caused by ageing is related to the damage at different levels of the auditory system (central and peripheral). Histologically, the aged cochlea shows degeneration of the stria vascularis, the sensorineural epithelium, and neurons of the central auditory pathways. The mechanisms responsible for age-associated hearing loss are still incompletely characterized. This work aims to give a broad overview of the scientific findings related to presbycusis, focusing mainly on experimental studies in animal models. Copyright © 2011 Elsevier Inc. All rights reserved.
Hoffmann, Sebastian; Kleinstreuer, Nicole; Alépée, Nathalie; Allen, David; Api, Anne Marie; Ashikaga, Takao; Clouet, Elodie; Cluzel, Magalie; Desprez, Bertrand; Gellatly, Nichola; Goebel, Carsten; Kern, Petra S; Klaric, Martina; Kühnl, Jochen; Lalko, Jon F; Martinozzi-Teissier, Silvia; Mewes, Karsten; Miyazawa, Masaaki; Parakhia, Rahul; van Vliet, Erwin; Zang, Qingda; Petersohn, Dirk
Cosmetics Europe, the European Trade Association for the cosmetics and personal care industry, is conducting a multi-phase program to develop regulatory accepted, animal-free testing strategies enabling the cosmetics industry to conduct safety assessments. Based on a systematic evaluation of test methods for skin sensitization, five non-animal test methods (DPRA (Direct Peptide Reactivity Assay), KeratinoSens TM , h-CLAT (human cell line activation test), U-SENS TM , SENS-IS) were selected for inclusion in a comprehensive database of 128 substances. Existing data were compiled and completed with newly generated data, the latter amounting to one-third of all data. The database was complemented with human and local lymph node assay (LLNA) reference data, physicochemical properties and use categories, and thoroughly curated. Focused on the availability of human data, the substance selection resulted nevertheless resulted in a high diversity of chemistries in terms of physico-chemical property ranges and use categories. Predictivities of skin sensitization potential and potency, where applicable, were calculated for the LLNA as compared to human data and for the individual test methods compared to both human and LLNA reference data. In addition, various aspects of applicability of the test methods were analyzed. Due to its high level of curation, comprehensiveness, and completeness, we propose our database as a point of reference for the evaluation and development of testing strategies, as done for example in the associated work of Kleinstreuer et al. We encourage the community to use it to meet the challenge of conducting skin sensitization safety assessment without generating new animal data.
Mirmehrabi, Mahmoud; Rohani, Sohrab; Perry, Luisa
A new activity coefficient model was developed from excess Gibbs free energy in the form G(ex) = cA(a) x(1)(b)...x(n)(b). The constants of the proposed model were considered to be function of solute and solvent dielectric constants, Hildebrand solubility parameters and specific volumes of solute and solvent molecules. The proposed model obeys the Gibbs-Duhem condition for activity coefficient models. To generalize the model and make it as a purely predictive model without any adjustable parameters, its constants were found using the experimental activity coefficient and physical properties of 20 vapor-liquid systems. The predictive capability of the proposed model was tested by calculating the activity coefficients of 41 binary vapor-liquid equilibrium systems and showed good agreement with the experimental data in comparison with two other predictive models, the UNIFAC and Hildebrand models. The only data used for the prediction of activity coefficients, were dielectric constants, Hildebrand solubility parameters, and specific volumes of the solute and solvent molecules. Furthermore, the proposed model was used to predict the activity coefficient of an organic compound, stearic acid, whose physical properties were available in methanol and 2-butanone. The predicted activity coefficient along with the thermal properties of the stearic acid were used to calculate the solubility of stearic acid in these two solvents and resulted in a better agreement with the experimental data compared to the UNIFAC and Hildebrand predictive models.
Animal models of psychiatric disorders are usually discussed with regard to three criteria first elaborated by Willner; face, predictive and construct validity. Here, we draw the history of these concepts and then try to redraw and refine these criteria, using the framework of the diathesis model of depression that has been proposed by several authors. We thus propose a set of five major criteria (with sub-categories for some of them); homological validity (including species validity and strain validity), pathogenic validity (including ontopathogenic validity and triggering validity), mechanistic validity, face validity (including ethological and biomarker validity) and predictive validity (including induction and remission validity). Homological validity requires that an adequate species and strain be chosen: considering species validity, primates will be considered to have a higher score than drosophila, and considering strains, a high stress reactivity in a strain scores higher than a low stress reactivity in another strain. Pathological validity corresponds to the fact that, in order to shape pathological characteristics, the organism has been manipulated both during the developmental period (for example, maternal separation: ontopathogenic validity) and during adulthood (for example, stress: triggering validity). Mechanistic validity corresponds to the fact that the cognitive (for example, cognitive bias) or biological mechanisms (such as dysfunction of the hormonal stress axis regulation) underlying the disorder are identical in both humans and animals. Face validity corresponds to the observable behavioral (ethological validity) or biological (biomarker validity) outcomes: for example anhedonic behavior (ethological validity) or elevated corticosterone (biomarker validity). Finally, predictive validity corresponds to the identity of the relationship between the triggering factor and the outcome (induction validity) and between the effects of the treatments
Yao, Benjamin Z; Nie, Bruce X; Liu, Zicheng; Zhu, Song-Chun
This paper presents animated pose templates (APTs) for detecting short-term, long-term, and contextual actions from cluttered scenes in videos. Each pose template consists of two components: 1) a shape template with deformable parts represented in an And-node whose appearances are represented by the Histogram of Oriented Gradient (HOG) features, and 2) a motion template specifying the motion of the parts by the Histogram of Optical-Flows (HOF) features. A shape template may have more than one motion template represented by an Or-node. Therefore, each action is defined as a mixture (Or-node) of pose templates in an And-Or tree structure. While this pose template is suitable for detecting short-term action snippets in two to five frames, we extend it in two ways: 1) For long-term actions, we animate the pose templates by adding temporal constraints in a Hidden Markov Model (HMM), and 2) for contextual actions, we treat contextual objects as additional parts of the pose templates and add constraints that encode spatial correlations between parts. To train the model, we manually annotate part locations on several keyframes of each video and cluster them into pose templates using EM. This leaves the unknown parameters for our learning algorithm in two groups: 1) latent variables for the unannotated frames including pose-IDs and part locations, 2) model parameters shared by all training samples such as weights for HOG and HOF features, canonical part locations of each pose, coefficients penalizing pose-transition and part-deformation. To learn these parameters, we introduce a semi-supervised structural SVM algorithm that iterates between two steps: 1) learning (updating) model parameters using labeled data by solving a structural SVM optimization, and 2) imputing missing variables (i.e., detecting actions on unlabeled frames) with parameters learned from the previous step and progressively accepting high-score frames as newly labeled examples. This algorithm belongs to a
Raphael Silveira Amaro
Full Text Available In the last decades, a remarkable number of models, variants from the Autoregressive Conditional Heteroscedastic family, have been developed and empirically tested, making extremely complex the process of choosing a particular model. This research aim to compare the predictive capacity, using the Model Confidence Set procedure, than five conditional heteroskedasticity models, considering eight different statistical probability distributions. The financial series which were used refers to the log-return series of the Bovespa index and the Dow Jones Industrial Index in the period between 27 October 2008 and 30 December 2014. The empirical evidences showed that, in general, competing models have a great homogeneity to make predictions, either for a stock market of a developed country or for a stock market of a developing country. An equivalent result can be inferred for the statistical probability distributions that were used.
Abramowitch, Steven D; Feola, Andrew; Jallah, Zegbeh; Moalli, Pamela A
Pelvic floor disorders such as pelvic organ prolapse, urinary incontinence, and fecal incontinence affect a large number of women each year. The pelvic floor can be thought of as a biomechanical structure due to the complex interaction between the vagina and its supportive structures that are designed to withstand the downward descent of the pelvic organs in response to increases in abdominal pressure. Although previous work has highlighted the biochemical changes that are associated with specific risk factors (i.e. parity, menopause, and genetics), little work has been done to understand the biomechanical changes that occur within the vagina and its supportive structures to prevent the onset of these pelvic floor disorders. Human studies are often limited due to the challenges of obtaining large tissue samples and ethical concerns. Therefore, it is necessary to investigate the use of animal models and their importance in understanding how different risk factors affect the biomechanical properties of the vagina and its supportive structures. In this review paper, we will discuss the different animal models that have been previously used to characterize the biomechanical properties of the vagina: including non-human primates, rodents, rabbits, and sheep. The anatomy and preliminary biomechanical findings are discussed along with the importance of considering experimental conditions, tissue anisotropy, and viscoelasticity when characterizing the biomechanical properties of vaginal tissue. Although there is not a lot of biomechanics research related to the vagina and pelvic floor, the future is exciting due to the significant potential for scientific findings that will improve our understanding of these conditions and hopefully lead to improvements in the prevention and treatment of pelvic disorders.
Gagic, Vesna; Bartomeus, Ignasi; Jonsson, Tomas; Taylor, Astrid; Winqvist, Camilla; Fischer, Christina; Slade, Eleanor M; Steffan-Dewenter, Ingolf; Emmerson, Mark; Potts, Simon G; Tscharntke, Teja; Weisser, Wolfgang; Bommarco, Riccardo
Drastic biodiversity declines have raised concerns about the deterioration of ecosystem functions and have motivated much recent research on the relationship between species diversity and ecosystem functioning. A functional trait framework has been proposed to improve the mechanistic understanding of this relationship, but this has rarely been tested for organisms other than plants. We analysed eight datasets, including five animal groups, to examine how well a trait-based approach, compared with a more traditional taxonomic approach, predicts seven ecosystem functions below- and above-ground. Trait-based indices consistently provided greater explanatory power than species richness or abundance. The frequency distributions of single or multiple traits in the community were the best predictors of ecosystem functioning. This implies that the ecosystem functions we investigated were underpinned by the combination of trait identities (i.e. single-trait indices) and trait complementarity (i.e. multi-trait indices) in the communities. Our study provides new insights into the general mechanisms that link biodiversity to ecosystem functioning in natural animal communities and suggests that the observed responses were due to the identity and dominance patterns of the trait composition rather than the number or abundance of species per se. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
2) and in animal models of human autoimmune diseases including autoimmune colitis (3), experimental autoimmune encephalomyelitis (4), collagen...studied in multiple pre-clinical animal models of autoimmune. For example, FTS can attenuate disease manifestations in experimental autoimmune... experimental animal model of polyarthritis, which can be induced in inbred Lewis rats by immunization with Complete Freund’s adjuvant containing
Infants and children with tuberculosis (TB) account for more than 20% of cases in endemic countries. Current animal models study TB during adulthood but animal models for adolescent and infant TB are scarce. Here we propose that minipigs can be used as an animal model to study adult, adolescent and ...
Bensdorp, Alexandra J; van der Steeg, Jan Willem; Steures, Pieternel; Habbema, J Dik F; Hompes, Peter G A; Bossuyt, Patrick M M; van der Veen, Fulco; Mol, Ben W J; Eijkemans, Marinus J C
One of the aims in reproductive medicine is to differentiate between couples that have favourable chances of conceiving naturally and those that do not. Since the development of the prediction model of Hunault, characteristics of the subfertile population have changed. The objective of this analysis was to assess whether additional predictors can refine the Hunault model and extend its applicability. Consecutive subfertile couples with unexplained and mild male subfertility presenting in fertility clinics were asked to participate in a prospective cohort study. We constructed a multivariable prediction model with the predictors from the Hunault model and new potential predictors. The primary outcome, natural conception leading to an ongoing pregnancy, was observed in 1053 women of the 5184 included couples (20%). All predictors of the Hunault model were selected into the revised model plus an additional seven (woman's body mass index, cycle length, basal FSH levels, tubal status,history of previous pregnancies in the current relationship (ongoing pregnancies after natural conception, fertility treatment or miscarriages), semen volume, and semen morphology. Predictions from the revised model seem to concur better with observed pregnancy rates compared with the Hunault model; c-statistic of 0.71 (95% CI 0.69 to 0.73) compared with 0.59 (95% CI 0.57 to 0.61). Copyright © 2017. Published by Elsevier Ltd.
Mirkovic, Djordje; Stepanian, Phillip M.; Kelly, Jeffrey F.; Chilson, Phillip B.
The radar scattering characteristics of aerial animals are typically obtained from controlled laboratory measurements of a freshly harvested specimen. These measurements are tedious to perform, difficult to replicate, and typically yield only a small subset of the full azimuthal, elevational, and polarimetric radio scattering data. As an alternative, biological applications of radar often assume that the radar cross sections of flying animals are isotropic, since sophisticated computer models are required to estimate the 3D scattering properties of objects having complex shapes. Using the method of moments implemented in the WIPL-D software package, we show for the first time that such electromagnetic modeling techniques (typically applied to man-made objects) can accurately predict organismal radio scattering characteristics from an anatomical model: here the Brazilian free-tailed bat (Tadarida brasiliensis). The simulated scattering properties of the bat agree with controlled measurements and radar observations made during a field study of bats in flight. This numerical technique can produce the full angular set of quantitative polarimetric scattering characteristics, while eliminating many practical difficulties associated with physical measurements. Such a modeling framework can be applied for bird, bat, and insect species, and will help drive a shift in radar biology from a largely qualitative and phenomenological science toward quantitative estimation of animal densities and taxonomic identification.
Full Text Available Louise Kruse Johansen, Henrik Elvang JensenDepartment of Veterinary Disease Biology, Faculty of Health and Medical Science, University of Copenhagen, Frederiksberg, DenmarkAbstract: Hematogenous osteomyelitis (HO, especially due to Staphylococcus aureus, is primarily reported in children and occurs when blood-borne bacteria settle in the metaphysis of a long bone and mediate an inflammatory response. The literature contains several reports on animal models aiming to simulate pediatric HO, in order to investigate the pathogenesis and for therapeutic use. In these models, osteomyelitis lesions develop subsequently to bacteremia, which can be induced by either intravenous or intra-arterial inoculation of bacteria. Intravenous inoculation is not optimal because of the ethical aspects of the extensive systemic reaction and the unpredictable identity of bones being infected. Also, intravenous inoculation often has to be combined with the induction of artificial bone necrosis in order to have macroscopic lesions. In contrast, models based on intra-arterial inoculation and subsequent development of local osteomyelitis, are the most accurate and predictable way to extrapolate to pediatric cases of HO. The most commonly used animal species for modeling of HO are rabbits, chickens, and mice, whereas, less frequently, dogs, rats, and pigs have been applied. The use of intra-arterial inoculation, without simultaneous artificial bone necrosis for the development of HO lesions has only been used in porcine models. Because of the similarity of human and porcine physiology, metabolic rate, and size, porcine models of HO are advantageous. Therefore, porcine models based on the intra-arterial induction of osteomyelitis are the most refined HO models.Keywords: hematogenous osteomyelitis, animal models, Staphylococcus aureus
Graham, Melanie L; Prescott, Mark J
Ethics on animal use in science in Western society is based on utilitarianism, weighing the harms and benefits to the animals involved against those of the intended human beneficiaries. The 3Rs concept (Replacement, Reduction, Refinement) is both a robust framework for minimizing animal use and suffering (addressing the harms to animals) and a means of supporting high quality science and translation (addressing the benefits). The ambiguity of basic research performed early in the research continuum can sometimes make harm-benefit analysis more difficult since anticipated benefit is often an incremental contribution to a field of knowledge. On the other hand, benefit is much more evident in translational research aimed at developing treatments for direct application in humans or animals suffering from disease. Though benefit may be easier to define, it should certainly not be considered automatic. Issues related to model validity seriously compromise experiments and have been implicated as a major impediment in translation, especially in complex disease models where harms to animals can be intensified. Increased investment and activity in the 3Rs is delivering new research models, tools and approaches with reduced reliance on animal use, improved animal welfare, and improved scientific and predictive value. Copyright © 2015 Elsevier B.V. All rights reserved.
Graham, Melanie L.; Prescott, Mark J.
Ethics on animal use in science in Western society is based on utilitarianism, weighing the harms and benefits to the animals involved against those of the intended human beneficiaries. The 3Rs concept (Replacement, Reduction, Refinement) is both a robust framework for minimizing animal use and suffering (addressing the harms to animals) and a means of supporting high quality science and translation (addressing the benefits). The ambiguity of basic research performed early in the research continuum can sometimes make harm-benefit analysis more difficult since anticipated benefit is often an incremental contribution to a field of knowledge. On the other hand, benefit is much more evident in translational research aimed at developing treatments for direct application in humans or animals suffering from disease. Though benefit may be easier to define, it should certainly not be considered automatic. Issues related to model validity seriously compromise experiments and have been implicated as a major impediment in translation, especially in complex disease models where harms to animals can be intensified. Increased investment and activity in the 3Rs is delivering new research models, tools and approaches with reduced reliance on animal use, improved animal welfare, and improved scientific and predictive value. PMID:25823812
Malik Abu Rafee
Full Text Available The overwhelming use of rat models in nerve regeneration studies is likely to induce skewness in treatment outcomes. To address the problem, this study was conducted in 8 adult guinea pigs of either sex to investigate the suitability of guinea pig as an alternative model for nerve regeneration studies. A crush injury was inflicted to the sciatic nerve of the left limb, which led to significant decrease in the pain perception and neurorecovery up to the 4th weak. Lengthening of foot print and shortening of toe spread were observed in the paw after nerve injury. A 3.49 ± 0.35 fold increase in expression of neuropilin 1 (NRP1 gene and 2.09 ± 0.51 fold increase in neuropilin 2 (NRP2 gene were recorded 1 week after nerve injury as compared to the normal nerve. Ratios of gastrocnemius muscle weight and volume of the experimental limb to control limb showed more than 50% decrease on the 30th day. Histopathologically, vacuolated appearance of the nerve was observed with presence of degenerated myelin debris in digestion chambers. Gastrocnemius muscle also showed degenerative changes. Scanning electron microscopy revealed loose and rough arrangement of connective tissue fibrils and presence of large spherical globules in crushed sciatic nerve. The findings suggest that guinea pigs could be used as an alternative animal model for nerve regeneration studies and might be preferred over rats due to their cooperative nature while recording different parameters.
Charmaine Y Pietersen
Full Text Available Schizophrenia is often associated with emotional blunting--the diminished ability to respond to emotionally salient stimuli--particularly those stimuli representative of negative emotional states, such as fear. This disturbance may stem from dysfunction of the amygdala, a brain region involved in fear processing. The present article describes a novel animal model of emotional blunting in schizophrenia. This model involves interfering with normal fear processing (classical conditioning in rats by means of acute ketamine administration. We confirm, in a series of experiments comprised of cFos staining, behavioral analysis and neurochemical determinations, that ketamine interferes with the behavioral expression of fear and with normal fear processing in the amygdala and related brain regions. We further show that the atypical antipsychotic drug clozapine, but not the typical antipsychotic haloperidol nor an experimental glutamate receptor 2/3 agonist, inhibits ketamine's effects and retains normal fear processing in the amygdala at a neurochemical level, despite the observation that fear-related behavior is still inhibited due to ketamine administration. Our results suggest that the relative resistance of emotional blunting to drug treatment may be partially due to an inability of conventional therapies to target the multiple anatomical and functional brain systems involved in emotional processing. A conceptual model reconciling our findings in terms of neurochemistry and behavior is postulated and discussed.
The mv3d software allows the modeling and display of three dimensional objects in interpretative mode with animation possibility in real time. This system is intended for a graphical extension of a FORTH interpreter (implemented by CEA/IRDI/D.LETI/DEIN) in order to control a specific hardware (3.D card designed and implemented by DEIN) allowing the generation of three dimensional objects. The object description is carried out with a specific graphical language integrated in the FORTH interpreter. Objects are modeled using elementary solids called basic forms (cube, cone, cylinder...) assembled with classical geometric transformations (rotation, translation and scaling). These basic forms are approximated by plane polygonal facets further divided in triangles. Coordinates of the summits of triangles constitute the geometrical data. These are sent to the 3.D. card for processing and display. Performed processing are: geometrical transformations on display, hidden surface elimination, shading and clipping. The mv3d software is not an entire modeler but a simple, modular and extensible tool, to which other specific functions may be easily added such as: robots motion, collisions... (author) [fr
Full Text Available Autism is a neurodevelopmental disorder of social behavior, which is more common in males than in females. The causes of autism are unknown; there is evidence for a substantial genetic component, but it is likely that a combination of genetic, environmental and epigenetic factors contribute to its complex pathogenesis. Rodent models that mimic the behavioral deficits of autism can be useful tools for dissecting both the etiology and molecular mechanisms. This review discusses animal models of autism generated by prenatal or neonatal environmental challenges, including virus infection and exposure to valproic acid (VPA or stress. Studies of viral infection models suggest that interleukin-6 can influence fetal development and programming. Prenatal exposure to the histone deacetylase inhibitor VPA has been linked to autism in children, and male VPA-exposed rats exhibit a spectrum of autistic-like behaviors. The experience of prenatal stress produces male-specific behavioral abnormalities in rats. These effects may be mediated by epigenetic modifications such as DNA methylation and histone acetylation resulting in alterations to the transcriptome.
Riviere, J E; Gabrielsson, J; Fink, M; Mochel, J
The application of mathematical modeling to problems in animal health has a rich history in the form of pharmacokinetic modeling applied to problems in veterinary medicine. Advances in modeling and simulation beyond pharmacokinetics have the potential to streamline and speed-up drug research and development programs. To foster these goals, a series of manuscripts will be published with the following goals: (i) expand the application of modeling and simulation to issues in veterinary pharmacology; (ii) bridge the gap between the level of modeling and simulation practiced in human and veterinary pharmacology; (iii) explore how modeling and simulation concepts can be used to improve our understanding of common issues not readily addressed in human pharmacology (e.g. breed differences, tissue residue depletion, vast weight ranges among adults within a single species, interspecies differences, small animal species research where data collection is limited to sparse sampling, availability of different sampling matrices); and (iv) describe how quantitative pharmacology approaches could help understanding key pharmacokinetic and pharmacodynamic characteristics of a drug candidate, with the goal of providing explicit, reproducible, and predictive evidence for optimizing drug development plans, enabling critical decision making, and eventually bringing safe and effective medicines to patients. This study introduces these concepts and introduces new approaches to modeling and simulation as well as clearly articulate basic assumptions and good practices. The driving force behind these activities is to create predictive models that are based on solid physiological and pharmacological principles as well as adhering to the limitations that are fundamental to applying mathematical and statistical models to biological systems. © 2015 John Wiley & Sons Ltd.
Full Text Available Aim: The orogastric route is the most preferred application method in the vast majority of the animal experiments in which application can be achieved by adding the material to the water of the experiment animal, through an orogastric tube or with a surgically managed ostomy. Material and Method: This experiment was constructed with twelve male Sprague-Dawley rats which were randomly assigned to one of two groups consist of control group ( group C, n: 6 and tube gastrostomy group ( group TG, n: 6.A novel and simple gastrostomy tube was derivated from a silicone foley catheter. Tube gastrostomy apparatus was constituted with a silicone foley catheter (6 French. In the group TG an incision was performed, and the stomach was visualized. A 1 cm incision was made in the midline and opening of the peritoneum. Anchoring sutures were placed and anterior gastric wall was lifted. The gastric wall is then opened. The apparatus was placed into the stomach and pulled through from a tunnel under the skin and fixed to the lateral abdominal wall with a 2/0 silk suture. Result: The procedure was ended in the 10th day of experiment. No mortality was observed in group C. The rats were monitored daily and no abnormal behavior consists of self harming incision site, resistance to oral intake or attending to displace. There was statistically significant difference in increasing alanine transaminase level (p<0.05 and decrease in the total protein and body weight (p<0.05 at the group TG at the end of experiment. There was significant increase in urea levels in Group C (p<0.05 at the end of experiment. The statistically significant decrease was observed in the same period in group C between aspartate transaminase, albumin, total protein, and body weight (p<0.05. Glucose (p=0.047 and aspartate transaminase (p=0.050 level decrease changes and weight loose (p=0.034 from preoperative period to the end of the experiment between gastrostomy and laparotomy groups were
Full Text Available Animal tracking is a growing field in ecology and previous work has shown that simple speed filtering of tracking data is not sufficient and that improvement of tracking location estimates are possible. To date, this has required methods that are complicated and often time-consuming (state-space models, resulting in limited application of this technique and the potential for analysis errors due to poor understanding of the fundamental framework behind the approach. We describe and test an alternative and intuitive approach consisting of bootstrapping random walks biased by forward particles. The model uses recorded data accuracy estimates, and can assimilate other sources of data such as sea-surface temperature, bathymetry and/or physical boundaries. We tested our model using ARGOS and geolocation tracks of elephant seals that also carried GPS tags in addition to PTTs, enabling true validation. Among pinnipeds, elephant seals are extreme divers that spend little time at the surface, which considerably impact the quality of both ARGOS and light-based geolocation tracks. Despite such low overall quality tracks, our model provided location estimates within 4.0, 5.5 and 12.0 km of true location 50% of the time, and within 9, 10.5 and 20.0 km 90% of the time, for above, equal or below average elephant seal ARGOS track qualities, respectively. With geolocation data, 50% of errors were less than 104.8 km (<0.94 degrees, and 90% were less than 199.8 km (<1.80 degrees. Larger errors were due to lack of sea-surface temperature gradients. In addition we show that our model is flexible enough to solve the obstacle avoidance problem by assimilating high resolution coastline data. This reduced the number of invalid on-land location by almost an order of magnitude. The method is intuitive, flexible and efficient, promising extensive utilization in future research.
Research purpose: The purpose of this empirical paper was to examine the predictive performance of credit scoring systems in Taiwan. Motivation for the study: Corporate lending remains a major business line for financial institutions. However, in light of the recent global financial crises, it has become extremely important for financial institutions to implement rigorous means of assessing clients seeking access to credit facilities. Research design, approach and method: Using a data sample of 10 349 observations drawn between 1992 and 2010, logistic regression models were utilised to examine the predictive performance of credit scoring systems. Main findings: A test of Goodness of fit demonstrated that credit scoring models that incorporated the Taiwan Corporate Credit Risk Index (TCRI, micro- and also macroeconomic variables possessed greater predictive power. This suggests that macroeconomic variables do have explanatory power for default credit risk. Practical/managerial implications: The originality in the study was that three models were developed to predict corporate firms’ defaults based on different microeconomic and macroeconomic factors such as the TCRI, asset growth rates, stock index and gross domestic product. Contribution/value-add: The study utilises different goodness of fits and receiver operator characteristics during the examination of the robustness of the predictive power of these factors.
Gong, Tao; Shuai, Lan; Zhang, Menghan
We survey recent computer modelling research of language evolution, focusing on a rule-based model simulating the lexicon-syntax coevolution and an equation-based model quantifying the language competition dynamics. We discuss four predictions of these models: (a) correlation between domain-general abilities (e.g. sequential learning) and language-specific mechanisms (e.g. word order processing); (b) coevolution of language and relevant competences (e.g. joint attention); (c) effects of cultural transmission and social structure on linguistic understandability; and (d) commonalities between linguistic, biological, and physical phenomena. All these contribute significantly to our understanding of the evolutions of language structures, individual learning mechanisms, and relevant biological and socio-cultural factors. We conclude the survey by highlighting three future directions of modelling studies of language evolution: (a) adopting experimental approaches for model evaluation; (b) consolidating empirical foundations of models; and (c) multi-disciplinary collaboration among modelling, linguistics, and other relevant disciplines.
Salaets, Thomas; Gie, Andre; Tack, Bieke; Deprest, Jan; Toelen, Jaan
Bronchopulmonary dysplasia (BPD) remains a frequent and disabling consequence of preterm birth, despite the recent advances in neonatal intensive care. There is a need to further improve outcomes and many novel therapeutic or preventive strategies are therefore investigated in animal models. We discuss in this review the aspects of human BPD pathophysiology and phenotype, which ideally should be mimicked by an animal model for this disease. Prematurity remains the common denominator in the heterogeneous spectrum of human BPD, and preterm animal models thus have a clear translational advantage. Additional factors, like excessive oxygen, mechanical ventilation and infection, which frequently have been studied in animal models, can contribute to preterm lung injury however are not indispensable to develop BPD. The phenotype of human BPD is characterized by alveolar developmental arrest with extracellular matrix remodeling, signs of obstructive airway disease and pulmonary vascular disease. Many animal models mimic this phenotype and have their place in BPD research, but results should be interpreted bearing in mind the specific advantages and disadvantages of the model. Term mice and rats are well suited for basic explorative research on specific disease mechanisms, essential for the generation of new hypotheses, while the larger ventilated preterm baboons and lambs provide a good platform for the ultimate translation of these strategies towards clinical application. The preterm rabbit model seems a promising model as it the smallest model that includes a factor of prematurity and has a unique position between the small and large animal models. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Pedersen, Einar B.; Herbertsson, Hannes R.; Niemann, Henrik
The developments in solutions for management of urban drainage are of vital importance, as the amount of sewer water from urban areas continues to increase due to the increase of the world’s population and the change in the climate conditions. How a sewer network is structured, monitored and cont...... benchmark model. Due to the inherent constraints the applied approach is based on Model Predictive Control....... and controlled have thus become essential factors for efficient performance of waste water treatment plants. This paper examines methods for simplified modelling and controlling a sewer network. A practical approach to the problem is used by analysing simplified design model, which is based on the Barcelona...
Shahirinia, Amir; Hajizadeh, Amin; Yu, David C
predictive model of the wind speed aggregates the non-homogeneous distributions into a single continuous distribution. Therefore, the result is able to capture the variation among the probability distributions of the wind speeds at the turbines’ locations in a wind farm. More specifically, instead of using...... a wind speed distribution whose parameters are known or estimated, the parameters are considered as random whose variations are according to probability distributions. The Bayesian predictive model for a Rayleigh which only has a single model scale parameter has been proposed. Also closed-form posterior......One of the major challenges with the increase in wind power generation is the uncertain nature of wind speed. So far the uncertainty about wind speed has been presented through probability distributions. Also the existing models that consider the uncertainty of the wind speed primarily view...
Kattan, Michael W; Gerds, Thomas A
system (i.e. old or new), such as the level of evidence for one or more factors included in the system or the general opinions of expert clinicians. However, given the major objective of estimating prognosis on an ordinal scale, we argue that the rival staging system candidates should be compared...... on their ability to predict outcome. We sought to outline an algorithm that would compare two rival ordinal systems on their predictive ability. RESULTS: We devised an algorithm based largely on the concordance index, which is appropriate for comparing two models in their ability to rank observations. We...... demonstrate our algorithm with a prostate cancer staging system example. CONCLUSION: We have provided an algorithm for selecting the preferred staging system based on prognostic accuracy. It appears to be useful for the purpose of selecting between two ordinal prediction models....
Predictive analytics can be used to rapidly spot hard-to-identify opportunities to better manage care--a key tool in accountable care. When considering analytics models, healthcare providers should: Make value-based care a priority and act on information from analytics models. Create a road map that includes achievable steps, rather than major endeavors. Set long-term expectations and recognize that the effectiveness of an analytics program takes time, unlike revenue cycle initiatives that may show a quick return.
Maldonado, A.G.; Rothenberg, G.
Predictive modeling has become a practical research tool in homogeneous catalysis. It can help to pinpoint ‘good regions’ in the catalyst space, narrowing the search for the optimal catalyst for a given reaction. Just like any other new idea, in silico catalyst optimization is accepted by some
Hu, Jiefeng; Zhu, Jianguo; Guerrero, Josep M.
required to realise high-performance of distributed generations and will realise innovative control techniques utilising model predictive control (MPC) to assist in coordinating the plethora of generation and load combinations, thus enable the effective exploitation of the clean renewable energy sources...
Batina, Ivo; Stoorvogel, Antonie Arij; Weiland, Siep
In this paper we present a further development of an algorithm for stochastic disturbance rejection in model predictive control with input constraints based on randomized algorithms. The algorithm presented in our work can solve the problem of stochastic disturbance rejection approximately but with
Ackmece, A. Behcet; Carson, John M., III
A model predictive control (MPC) algorithm that differs from prior MPC algorithms has been developed for controlling an uncertain nonlinear system. This algorithm guarantees the resolvability of an associated finite-horizon optimal-control problem in a receding-horizon implementation.
Bendtsen, Jan Dimon; Trangbæk, K; Stoustrup, Jakob
This paper deals with hierarchichal model predictive control (MPC) of distributed systems. A three level hierachical approach is proposed, consisting of a high level MPC controller, a second level of so-called aggregators, controlled by an online MPC-like algorithm, and a lower level of autonomous...
Prasath, Guru; Jørgensen, John Bagterp
We develop a regularized l2 finite impulse response (FIR) predictive controller with input and input-rate constraints. Feedback is based on a simple constant output disturbance filter. The performance of the predictive controller in the face of plant-model mismatch is investigated by simulations ...
Elsy Nalleli Loria-Cervera
Full Text Available Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail are being infected, and different numbers (“low” 1×102 and “high” 1×106 of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.
Hensley, Christopher; Tallichet, Suzanne E; Dutkiewicz, Erik L
The present study seeks to replicate Tallichet, Hensley, and Singer's research on childhood animal cruelty methods by using a sample of 180 male inmates surveyed at both medium- and maximum-security prisons in a southern state. The purpose of the current study was to first reexamine the relationship between demographic and situational factors and specific methods of childhood animal cruelty. Second, the correlation between an abuser's chosen method(s) of childhood animal cruelty on later recurrent acts of adult violent crimes was reinvestigated. Regression analyses revealed that respondents who engaged in frequent animal cruelty were more likely to have drowned, shot, kicked, or had sex with animals. Those who had grown up in urban areas and those who did not become upset after abusing animals were more likely to have kicked animals. Respondents who covered up their abuse were more likely to have had sex with animals. Sex with animals was the only method of childhood animal cruelty that predicted the later commission of adult violent crimes.
Full Text Available Autism spectrum disorders (ASD are a complex neurodevelopmental disorder that display a triad of core behavioral deficits including restricted interests, often accompanied by repetitive behavior, deficits in language and communication, and an inability to engage in reciprocal social interactions. ASD is among the most heritable disorders but is not a simple disorder with a singular pathology and has a rather complex etiology. It is interesting to note that perturbations in synaptic growth, development and stability underlie a variety of neuropsychiatric disorders, including ASD, schizophrenia, epilepsy and intellectual disability. Biological characterization of an increasing repertoire of synaptic mutants in various model organisms indicates synaptic dysfunction as causal in the pathophysiology of ASD. Our understanding of the genes and genetic pathways that contribute towards the formation, stabilization and maintenance of functional synapses coupled with an in-depth phenotypic analysis of the cellular and behavioral characteristics is therefore essential to unraveling the pathogenesis of these disorders. In this review, we discuss the genetic aspects of ASD emphasizing on the well conserved set of genes and genetic pathways implicated in this disorder, many of which contribute to synapse assembly and maintenance across species. We also review how fundamental research using animal models is providing key insights into the various facets of human ASD.
Bharathi S. Gadad
Full Text Available Autism is a heterogeneous behaviorally defined neurodevelopmental disorder. It is defined by the presence of marked social deficits, specific language abnormalities, and stereotyped repetitive patterns of behavior. Because of the variability in the behavioral phenotype of the disorder among patients, the term autism spectrum disorder has been established. In the first part of this review, we provide an overview of neuropathological findings from studies of autism postmortem brains and identify the cerebellum as one of the key brain regions that can play a role in the autism phenotype. We review research findings that indicate possible links between the environment and autism including the role of mercury and immune-related factors. Because both genes and environment can alter the structure of the developing brain in different ways, it is not surprising that there is heterogeneity in the behavioral and neuropathological phenotypes of autism spectrum disorders. Finally, we describe animal models of autism that occur following insertion of different autism-related genes and exposure to environmental factors, highlighting those models which exhibit both autism-like behavior and ne