MINI REVIEW ARTICLE
published: 04 March 2015
doi: 10.3389/fnins.2015.00064
Lessons from the analysis of nonhuman primates for
understanding human aging and neurodegenerative
diseases
Jean-Michel Verdier 1,2,3*, Isabelle Acquatella 1,2,3, Corinne Lautier 1,2,3, Gina Devau 1,2,3,
Stéphanie Trouche 1,2,3, Christelle Lasbleiz 1,2,3 and Nadine Mestre-Francés 1,2,3
1 Université de Montpellier, Montpellier, France
2 Institut National de la Santé et de la Recherche Médicale, U1198, Montpellier, France
3 Ecole Pratique des Hautes Etudes, Paris, France
Edited by:
Patrick Lewis, University of Reading,
UK
Reviewed by:
Ricardo Insausti, University of
Castilla -la Mancha, Spain
Varun Kesherwani, University of
Nebraska Medical Center, USA
*Correspondence:
Jean-Michel Verdier, University of
Montpellier, Place Eugène Bataillon,
CC105, 34095 Montpellier, France
e-mail: [email protected]
univ-montp2.fr
Animal models are necessary tools for solving the most serious challenges facing medical
research. In aging and neurodegenerative disease studies, rodents occupy a place of
choice. However, the most challenging questions about longevity, the complexity and
functioning of brain networks or social intelligence can almost only be investigated in
nonhuman primates. Beside the fact that their brain structure is much closer to that of
humans, they develop highly complex cognitive strategies and they are visually-oriented
like humans. For these reasons, they deserve consideration, although their management
and care are more complicated and the related costs much higher. Despite these caveats,
considerable scientific advances have been possible using nonhuman primates. This
review concisely summarizes their role in the study of aging and of the mechanisms
involved in neurodegenerative disorders associated mainly with cognitive dysfunctions
(Alzheimer’s and prion diseases) or motor deficits (Parkinson’s and related diseases).
Keywords: neuroscience, brain, aging, neurodegenerative diseases, nonhuman primate
WHY DO WE NEED ANIMAL MODELS?
The simplest answer to this question is to increase our general
knowledge, to experimentally test theories. Animal model use-
fulness is manifold, from the study of physiological processes to
the identification of disease-causing mechanisms. Indeed, phys-
iopathological studies are of the utmost importance for develop-
ing diagnostic and therapeutic approaches based on the discovery
of new, more sensitive and specific biomarkers, the identifica-
tion of the mechanism of action of drugs, the establishment of
pharmacodynamics and pharmacokinetic parameters, the toxic-
ity analysis of new compounds or the assessment of clinical drug
regimens.
Many different animal models, ranging from unicellular
organisms (bacteria, yeast) to invertebrates (the roundworm
Caenorhabditis elegans or the fruit fly Drosophila melanogaster)
and vertebrates (fish and mammals), are currently used for
research on aging and neurodegenerative disorders. T ...
Researchers use animal models in basic research, in developing new therapeutic strategies for treating human diseases, and in drug discovery research (including target identification and validation, drug screening and lead optimization, and toxicity and safety screening), as well as in preclinical studies of drug safety and efficacy.
This document proposes a new interdisciplinary field called "Endogenous archaeology" that examines physiological processes from an evolutionary perspective. It suggests analyzing areas like neuroscience, immunology, and genetics through an archaeological lens to better understand how ancient evolutionary influences still impact human biology today. Examples mentioned include how opioid receptors relate to ancestral exposure to opioids in plants, circadian rhythms relating to ancestral eating patterns, and vestigial structures providing insight into human evolutionary history. The field aims to integrate evidence from areas like paleontology, genetics, and neuroscience to develop a more holistic understanding of human physiology and behavior through the lens of the evolutionary processes that shaped human biology.
Animal Models from The Concise Corsini Encyclopedia of Ps.docxjustine1simpson78276
Animal Models
from The Concise Corsini Encyclopedia of Psychology and Behavioral Science
When medical or psychological phenomena in animals are studied as analogues to those
phenomena in humans, one is said to be using an animal model. Models are basic and powerful
tools in biological and behavioral sciences, and this explains in part why so much research aimed
at understanding human physiology, brain, and behavior is actually done with animals. The key
word for understanding models is analogy. Use of a model is not a claim of identity with that
being modeled. Rather, a model is a convergent set of analogies between the human phenomenon
and the system that is being studied as a model for that phenomenon. Animal models are widely
used in neuroscience and psychology to explore and understand new relationships and
interactions among the environment, central nervous system, and behavior and to study these
interrelations under simpler and more controlled conditions than can be achieved
in research with humans. Animals models often allow for the discovery of causal relations not
possible in research on humans.
Animal models have a long and distinguished history in studies of both normal and abnormal
behavior. Life scientists (e.g., anatomists, physiologists, pharmacologists, and psychologists)
broadly accept the homological and analogical bases for the use of animal models that are rooted
in the evolutionary theory of Charles Darwin. Evolutionary theory projects a continuity of
morphology, physiology, and the emergent emotions and ÒmindÓ from animals to humans.
At the more biological end of the continuum of behavioral neuroscience and
psychological research and application, the use of animal models finds general acceptance and is
largely noncontroversial. These uses include research on neural mechanisms of reflexes,
motivation, emotion, learning, perception, and memory. Animal models are an established
integral component of the progress of understanding in these areas. Contemporary animal models
make clear that neuroscience, emotion, and behavior do not exist in a linear chain from one to
the other but in a continuously interdependent interacting circle. More
controversially, animal models have been and continue to be extended with success into the
behavioral neuroscience of memory dysfunction in aging, problem solving and thinking, social
interactions and cultural structures, drug dependency and addiction, psychopharmacology, and
psychiatry.
Animal modeling is more difficult and controversial when it addresses dysfunctional behavior
and psychopathology. Animal models promise an understanding of human psychopathology, not
as bizarre distortions of behavior but, rather, as the consequence of lawful psychological
processes whose principles and mechanisms can be elucidated scientifically. Ivan Pavlov was
perhaps the first to argue that experimentally induced abnormal behavior in anim.
This document proposes a new field of "Endogenous Archeology" that aims to classify and better understand physiological processes by viewing them through an evolutionary lens. It summarizes evidence from various scientific disciplines like anatomy, neuroscience, and genetics that suggest human physiology and behavior are influenced by ancient, evolutionary processes. The document provides numerous examples from human and animal biology to support analyzing current functions through their ancestral origins. It concludes by calling for an open research project involving experts from different fields to further develop and analyze the potential of this new "Endogenous Archeology" discipline.
This document discusses various animal models and their ability to predict human outcomes. It notes that while animal models in pathophysiology and toxicology can be used to predict human responses, whether animals accurately predict human response to drugs and chemicals is controversial. The document analyzes different animal models empirically using scientific tools to determine how well they can predict human responses.
This document discusses the potential for a new field of "Endogenous Archeology" that uses evidence from human evolution and physiology to better understand modern human behavior, biology, and disease. It provides examples from various scientific disciplines like neuroscience, immunology, and genetics that could be studied through this lens. The document also reviews several studies that have analyzed human brain development and cognition through an evolutionary perspective, finding that brain shape became modern around 100,000-35,000 years ago as behaviors also emerged, suggesting genetic changes impacted early brain growth. This new field could integrate evidence across many areas to develop a more holistic understanding of the ancient origins and archeological processes still present in human mind, body, and disease today.
Contributions of Neuroscience toOur Understanding of CognitiAlleneMcclendon878
Contributions of Neuroscience to
Our Understanding of Cognitive
Development
Adele Diamond1 and Dima Amso2
1
Department of Psychiatry, University of British Columbia, and Department of Child and Adolescent Psychiatry,
BC Children’s Hospital, Vancouver, Canada; and
2
Sackler Institute for Developmental Psychobiology,
Weill Medical College of Cornell University
ABSTRACT—One major contribution of neuroscience to
understanding cognitive development has been in demon-
strating that biology is not destiny—that is, demonstrating
the remarkable role of experience in shaping the mind,
brain, and body. Only rarely has neuroscience provided
wholly new insights into cognitive development, but often
it has provided evidence of mechanisms by which obser-
vations of developmental psychologists could be explained.
Behavioral findings have often remained controversial
until an underlying biological mechanism for them was
offered. Neuroscience has demonstrated promise for de-
tecting cognitive problems before they are behaviorally
observable—and, hence, promise for early intervention. In
this article, we discuss examples drawn from imitation and
mirror neurons, phenylketonuria (PKU) and prefrontal
dopamine, maternal touch and stress reactivity, and non-
genetic (behavioral) intergenerational transmission of bi-
ological characteristics.
KEYWORDS—plasticity; epigenesis; mothering; executive
functions; animal models; molecular genetics; memory
Neuroscience research has made its greatest contributions to the
study of cognitive development by illuminating mechanisms
(providing a ‘‘how’’) that underlie behavioral observations made
earlier by psychologists. It has also made important contribu-
tions to our understanding of cognitive development by dem-
onstrating that the brain is far more plastic at all ages than
previously thought—and thus that the speed and extent by which
experience and behavior can shape the brain is greater than al-
most anyone imagined. In other words, rather than showing that
biology is destiny, neuroscience research has been at the fore-
front of demonstrating the powerful role of experience throughout
life. Besides the surprising evidence of the remarkable extent
of experience-induced plasticity, rarely has neuroscience given
us previously unknown insights into cognitive development, but
neuroscience does offer promise of being able to detect some
problems before they are behaviorally observable.
PROVIDING MECHANISMS THAT CAN ACCOUNT FOR
BEHAVIORAL RESULTS REPORTED BY
PSYCHOLOGISTS
Here we describe two examples of behavioral findings by psy-
chologists that were largely ignored or extremely controversial
until underlying biological mechanisms capable of accounting
for them were provided by neuroscience research. One such
example concerns cognitive deficits documented in children
treated early and continuously for phenylketonuria (PKU). The
second example involves neonatal imitation observed b ...
This document summarizes animal models of anxiety in mice. It discusses both conditioned models, which involve pairing a neutral stimulus with an aversive event like electric shock, and unconditioned models, which involve a mouse's natural reactions to stress stimuli without pain or discomfort. Two commonly used unconditioned models are described in detail: the open field test, which measures thigmotaxis and exploration, and the elevated plus maze, which conflicts a mouse's natural aversion to open spaces with its drive to explore. The document notes issues with standardization and interpretation of these tests and stresses the importance of validating any animal model of anxiety.
Researchers use animal models in basic research, in developing new therapeutic strategies for treating human diseases, and in drug discovery research (including target identification and validation, drug screening and lead optimization, and toxicity and safety screening), as well as in preclinical studies of drug safety and efficacy.
This document proposes a new interdisciplinary field called "Endogenous archaeology" that examines physiological processes from an evolutionary perspective. It suggests analyzing areas like neuroscience, immunology, and genetics through an archaeological lens to better understand how ancient evolutionary influences still impact human biology today. Examples mentioned include how opioid receptors relate to ancestral exposure to opioids in plants, circadian rhythms relating to ancestral eating patterns, and vestigial structures providing insight into human evolutionary history. The field aims to integrate evidence from areas like paleontology, genetics, and neuroscience to develop a more holistic understanding of human physiology and behavior through the lens of the evolutionary processes that shaped human biology.
Animal Models from The Concise Corsini Encyclopedia of Ps.docxjustine1simpson78276
Animal Models
from The Concise Corsini Encyclopedia of Psychology and Behavioral Science
When medical or psychological phenomena in animals are studied as analogues to those
phenomena in humans, one is said to be using an animal model. Models are basic and powerful
tools in biological and behavioral sciences, and this explains in part why so much research aimed
at understanding human physiology, brain, and behavior is actually done with animals. The key
word for understanding models is analogy. Use of a model is not a claim of identity with that
being modeled. Rather, a model is a convergent set of analogies between the human phenomenon
and the system that is being studied as a model for that phenomenon. Animal models are widely
used in neuroscience and psychology to explore and understand new relationships and
interactions among the environment, central nervous system, and behavior and to study these
interrelations under simpler and more controlled conditions than can be achieved
in research with humans. Animals models often allow for the discovery of causal relations not
possible in research on humans.
Animal models have a long and distinguished history in studies of both normal and abnormal
behavior. Life scientists (e.g., anatomists, physiologists, pharmacologists, and psychologists)
broadly accept the homological and analogical bases for the use of animal models that are rooted
in the evolutionary theory of Charles Darwin. Evolutionary theory projects a continuity of
morphology, physiology, and the emergent emotions and ÒmindÓ from animals to humans.
At the more biological end of the continuum of behavioral neuroscience and
psychological research and application, the use of animal models finds general acceptance and is
largely noncontroversial. These uses include research on neural mechanisms of reflexes,
motivation, emotion, learning, perception, and memory. Animal models are an established
integral component of the progress of understanding in these areas. Contemporary animal models
make clear that neuroscience, emotion, and behavior do not exist in a linear chain from one to
the other but in a continuously interdependent interacting circle. More
controversially, animal models have been and continue to be extended with success into the
behavioral neuroscience of memory dysfunction in aging, problem solving and thinking, social
interactions and cultural structures, drug dependency and addiction, psychopharmacology, and
psychiatry.
Animal modeling is more difficult and controversial when it addresses dysfunctional behavior
and psychopathology. Animal models promise an understanding of human psychopathology, not
as bizarre distortions of behavior but, rather, as the consequence of lawful psychological
processes whose principles and mechanisms can be elucidated scientifically. Ivan Pavlov was
perhaps the first to argue that experimentally induced abnormal behavior in anim.
This document proposes a new field of "Endogenous Archeology" that aims to classify and better understand physiological processes by viewing them through an evolutionary lens. It summarizes evidence from various scientific disciplines like anatomy, neuroscience, and genetics that suggest human physiology and behavior are influenced by ancient, evolutionary processes. The document provides numerous examples from human and animal biology to support analyzing current functions through their ancestral origins. It concludes by calling for an open research project involving experts from different fields to further develop and analyze the potential of this new "Endogenous Archeology" discipline.
This document discusses various animal models and their ability to predict human outcomes. It notes that while animal models in pathophysiology and toxicology can be used to predict human responses, whether animals accurately predict human response to drugs and chemicals is controversial. The document analyzes different animal models empirically using scientific tools to determine how well they can predict human responses.
This document discusses the potential for a new field of "Endogenous Archeology" that uses evidence from human evolution and physiology to better understand modern human behavior, biology, and disease. It provides examples from various scientific disciplines like neuroscience, immunology, and genetics that could be studied through this lens. The document also reviews several studies that have analyzed human brain development and cognition through an evolutionary perspective, finding that brain shape became modern around 100,000-35,000 years ago as behaviors also emerged, suggesting genetic changes impacted early brain growth. This new field could integrate evidence across many areas to develop a more holistic understanding of the ancient origins and archeological processes still present in human mind, body, and disease today.
Contributions of Neuroscience toOur Understanding of CognitiAlleneMcclendon878
Contributions of Neuroscience to
Our Understanding of Cognitive
Development
Adele Diamond1 and Dima Amso2
1
Department of Psychiatry, University of British Columbia, and Department of Child and Adolescent Psychiatry,
BC Children’s Hospital, Vancouver, Canada; and
2
Sackler Institute for Developmental Psychobiology,
Weill Medical College of Cornell University
ABSTRACT—One major contribution of neuroscience to
understanding cognitive development has been in demon-
strating that biology is not destiny—that is, demonstrating
the remarkable role of experience in shaping the mind,
brain, and body. Only rarely has neuroscience provided
wholly new insights into cognitive development, but often
it has provided evidence of mechanisms by which obser-
vations of developmental psychologists could be explained.
Behavioral findings have often remained controversial
until an underlying biological mechanism for them was
offered. Neuroscience has demonstrated promise for de-
tecting cognitive problems before they are behaviorally
observable—and, hence, promise for early intervention. In
this article, we discuss examples drawn from imitation and
mirror neurons, phenylketonuria (PKU) and prefrontal
dopamine, maternal touch and stress reactivity, and non-
genetic (behavioral) intergenerational transmission of bi-
ological characteristics.
KEYWORDS—plasticity; epigenesis; mothering; executive
functions; animal models; molecular genetics; memory
Neuroscience research has made its greatest contributions to the
study of cognitive development by illuminating mechanisms
(providing a ‘‘how’’) that underlie behavioral observations made
earlier by psychologists. It has also made important contribu-
tions to our understanding of cognitive development by dem-
onstrating that the brain is far more plastic at all ages than
previously thought—and thus that the speed and extent by which
experience and behavior can shape the brain is greater than al-
most anyone imagined. In other words, rather than showing that
biology is destiny, neuroscience research has been at the fore-
front of demonstrating the powerful role of experience throughout
life. Besides the surprising evidence of the remarkable extent
of experience-induced plasticity, rarely has neuroscience given
us previously unknown insights into cognitive development, but
neuroscience does offer promise of being able to detect some
problems before they are behaviorally observable.
PROVIDING MECHANISMS THAT CAN ACCOUNT FOR
BEHAVIORAL RESULTS REPORTED BY
PSYCHOLOGISTS
Here we describe two examples of behavioral findings by psy-
chologists that were largely ignored or extremely controversial
until underlying biological mechanisms capable of accounting
for them were provided by neuroscience research. One such
example concerns cognitive deficits documented in children
treated early and continuously for phenylketonuria (PKU). The
second example involves neonatal imitation observed b ...
This document summarizes animal models of anxiety in mice. It discusses both conditioned models, which involve pairing a neutral stimulus with an aversive event like electric shock, and unconditioned models, which involve a mouse's natural reactions to stress stimuli without pain or discomfort. Two commonly used unconditioned models are described in detail: the open field test, which measures thigmotaxis and exploration, and the elevated plus maze, which conflicts a mouse's natural aversion to open spaces with its drive to explore. The document notes issues with standardization and interpretation of these tests and stresses the importance of validating any animal model of anxiety.
The document discusses several animal models used to study various aspects of cellular and molecular biology, including their applications to human health. Drosophila melanogaster is used to study the molecular causes and potential treatment of cardiac dysfunction in myotonic dystrophy. Researchers were able to reproduce symptoms of the disease in fruit flies and found that the drug pentamidine improved arrhythmias and contractility issues. Xenopus laevis is discussed as a model to better understand nerve tissue regeneration and neurogenesis through the study of brain-derived neurotrophic factor in stem cells of the olfactory epithelium. Various cellular models allow researchers to overcome the complexity of humans and apply findings to therapy.
This document summarizes a study of diagnostic processes in a neuro-oncology clinic in Israel. The study observed clinic operations for 6 months through participant observation and interviews. It finds that brain tumor diagnoses involve complex interactions between multiple experts, including neuro-oncologists, radiologists, pathologists, and others. Diagnoses are negotiated and refined over time through mechanisms like hierarchies of expertise, sequencing of tests, negotiations between experts, consideration of peripheral symptoms, and pragmatism in treatment decisions. Diagnoses are also fluid and lifelong processes as patients receive ongoing testing and care.
This document summarizes research on oxytocin and vasopressin in treating autism by comparing animal models to human studies. It reviews findings that oxytocin and vasopressin affect social bonding behaviors in animals like prairie voles and rats. Short-term oxytocin injections in animals increase non-specific social behaviors, while long-term injections can impair bonding abilities. Comparing these animal studies to human neuroimaging research helps explain the mechanisms and potential treatments for autism and other social disorders.
This study evaluated the validity of a rat model of obsessive-compulsive disorder (OCD) induced by neonatal exposure to neoclomipramine. Rats exposed to neoclomipramine as neonates were tested in a marble arena and hole board behavioral assay after administration of serotonin drugs. The study found that neonatally-exposed rats buried significantly more marbles than controls, supporting the face validity of the neoclomipramine model. There was also a significant interaction effect for marble checking behavior. This study provided further evidence for the validity of the neoclomipramine rat model of OCD.
This document is an abstract submission for a speech on common aspects in the physiological pathways of addiction and evolutionary processes that are useful for pharmaco-toxicological approaches. It discusses how certain neuronal circuits play a crucial role in addiction, learning, and reward mechanisms in mammals, as seen in behaviors like breastfeeding and parental care of offspring. Several studies are cited showing the involvement of dopamine and other neurotransmitters in addiction and natural reward processes, suggesting similarities that can help understand and potentially treat addiction.
The biological perspective views behavior as arising from physiological and genetic factors that interact with the environment. Key aspects of this perspective include Darwin's theory of evolution by natural selection, research on the brain and nervous system using methods like experiments and case studies, and theories about how genes and biological processes influence behavior. Studies have linked specific behaviors to brain regions and shown that splitting the brain's hemispheres can produce two separate streams of awareness, supporting the biological view that the brain determines behavior. Gender differences are also studied from this perspective in terms of both nature and nurture influences.
Applicability of mouse models to the study of human disease.pdfcarolinamurua1
Mice and humans share many genetic and physiological similarities but also have important differences that must be considered when using mouse models to study human disease. While mice and humans have a high degree of genetic similarity, their regulatory networks diverge significantly, especially regarding the immune system, metabolism, and stress responses. Physiologically, mice have higher metabolic rates, smaller organs and tissues, and differences in lung anatomy compared to humans. Immunologically, mice and humans differ in leukocyte proportions, T cell activation pathways, antibody subtypes, and responses to pathogens. A thorough understanding of these similarities and differences is necessary for meaningful interpretation and translation of mouse model experiments to human clinical applications.
This document summarizes research on the common neurobiological pathways involved in both mammalian parental care behaviors and addiction. It discusses how dopamine and other neurotransmitter systems regulate behaviors like breastfeeding and bonding in mammals, and how similar systems are implicated in addiction. Several studies are cited showing that drug addiction is associated with dysfunction of dopamine and reward pathways in the brain, similar to pathways involved in natural behaviors in mammals like parenting and bonding. The document concludes that understanding these evolutionary similarities can provide insights into the neurobiology of addiction.
The document summarizes a study that examined the grey matter of multiple sclerosis patients. The study found an absence of functional peroxisomes in the grey matter of multiple sclerosis patients. Peroxisomes help break down toxins and fatty acids in neural cells. The study used staining, gene expression analysis, and fatty acid quantification to show that multiple sclerosis grey matter has significantly fewer peroxisomes and accumulates more fatty acids compared to normal grey matter. As multiple sclerosis progresses, the levels of a peroxisome membrane protein called PMP70 decrease, indicating fewer peroxisomes over time. This absence of peroxisomes may contribute to multiple sclerosis progression by hindering neural cell function.
1) The document proposes a new interdisciplinary field called Endogenous Archeology that analyzes scientific literature related to human evolution to better understand physiological processes from an archeological perspective.
2) Key areas that could be studied include the amygdala and its role in behavior, mindset kinetics and depression, brain signal modulation, and hibernation physiology.
3) Evidence from studies on brain and cognitive evolution in humans and other species supports analyzing evolutionary processes through an endogenous archeological approach combining evidence from multiple disciplines.
Ontology based support for brain tumour study Subhashis Das
The document discusses building an ontology to support brain tumor study. It begins with background on brain tumors and issues with current information retrieval systems. The author then explains why ontology was chosen as a solution and the methodology used, which included identifying terminology, analyzing, synthesizing, and standardizing terms. The ontology structure with top-level branches for tumor types, symptoms, causes, and treatments is described. Potential uses for physicians and researchers are discussed.
This study examined functional connectivity of the medial temporal lobe (MTL) and its relation to learning and awareness. Participants completed a sensory learning task and were classified as AWARE or UNAWARE based on their ability to learn tone-visual stimulus associations. For AWARE participants, MTL activity correlated with learned discrimination and reversal, engaging dorsolateral prefrontal and occipital cortices. For UNAWARE participants, MTL activity correlated only with simple facilitation and engaged contralateral MTL, thalamus regions. This suggests the MTL contribution to learning depends on its pattern of interactions with other brain regions.
1) The document discusses a proposed new depurative-toxicological-pharmacological therapeutic strategy for certain spinal cord and brain degenerative and inflammatory diseases or acute trauma.
2) It notes several questions about common aspects of neurodegenerative diseases like accumulation of metabolic waste products and immune system involvement.
3) The strategy would use an informatics approach to address the problems and processes involved in these diseases. The goal is to submit a new treatment approach for evaluation by researchers.
A randomized controlled trial tested the effectiveness of environmental enrichment for treating autism symptoms in children aged 3-12. The enriched group received daily sensory stimulation exercises targeting olfaction and touch, while the control group received no enrichment. Testing showed the enriched group experienced significantly greater improvement on measures of autism severity and cognition compared to controls. Specifically, 42% of the enriched group versus 7% of controls showed clinically significant autism symptom improvement, and the enriched group's cognitive scores improved 11.3 points more on average. The majority of parents also reported overall symptom improvement for children in the enriched versus control group. Thus, environmental enrichment appears to be an effective treatment for ameliorating autism symptoms in children.
This document discusses the role of sex steroid hormones in schizophrenia based on animal model and human studies. It notes that schizophrenia occurs on average 1.5-4.5 years earlier in men than women, and that women with schizophrenia may have varying estrogen levels with the most severe phase occurring during periods of low estrogen. Dopamine plays a role in regulating sensorimotor filtration in both rodents and humans, and many studies have focused on the effects of administering estrogen and testosterone in schizophrenia.
CASE 6B – CHESTER & WAYNE Chester & Wayne is a regional .docxannandleola
CASE 6B – CHESTER & WAYNE
Chester & Wayne is a regional food distribution company. Mr. Chester, CEO, has asked your
assistance in preparing cash-flow information for the last three months of this year. Selected
accounts from an interim balance sheet dated September 30, have the following balances:
Cash $142,100 Accounts payable $354,155
Marketable securities 200,000 Other payables 53,200
Accounts receivable $1,012,500
Inventories 150,388
Mr. Wayne, CFO, provides you with the following information based on experience and
management policy. All sales are credit sales and are billed the last day of the month of sale.
Customers paying within 10 days of the billing date may take a 2 percent cash discount. Forty
percent of the sales is paid within the discount period in the month following billing. An
additional 25 percent pays in the same month but does not receive the cash discount. Thirty
percent is collected in the second month after billing; the remainder is uncollectible. Additional
cash of $24,000 is expected in October from renting unused warehouse space.
Sixty percent of all purchases, selling and administrative expenses, and advertising expenses is
paid in the month incurred. The remainder is paid in the following month. Ending inventory is
set at 25 percent of the next month's budgeted cost of goods sold. The company's gross profit
averages 30 percent of sales for the month. Selling and administrative expenses follow the
formula of 5 percent of the current month's sales plus $75,000, which includes depreciation of
$5,000. Advertising expenses are budgeted at 3 percent of sales.
Actual and budgeted sales information is as follows:
Actual: Budgeted:
August $750,000 October $826,800
September 787,500 November 868,200
December 911,600
January 930,000
The company will acquire equipment costing $250,000 cash in November. Dividends of $45,000
will be paid in December.
The company would like to maintain a minimum cash balance at the end of each month of
$120,000. Any excess amounts go first to repayment of short-term borrowings and then to
investment in marketable securities. When cash is needed to reach the minimum balance, the
company policy is to sell marketable securities before borrowing.
The company will acquire equipment costing $250,000 cash in November. Dividends of $45,000
will be paid in December.
The company would like to maintain a minimum cash balance at the end of each month of
$120,000. Any excess amounts go first to repayment of short-term borrowings and then to
investment in marketable securities. When cash is needed to reach the minimum balance, the
company policy is to sell marketable securities before borrowing.
Questions (use of spreadsheet software is recommended):
1. Prepare a cash budget for each month of the fourth quarter and for the quarter in total.
Prepare supporting schedules as needed. (Round all budge.
CASE 9 Bulimia Nervosa Table 9-1 Dx Checklist Bulimia Nervos.docxannandleola
"CASE 9 Bulimia Nervosa Table 9-1 Dx Checklist Bulimia Nervosa 1. Repeated binge-eating episodes. 2. Repeated performance of ill-advised compensatory behaviors (e.g., forced vomiting) to prevent weight gain. 3. Symptoms take place at least weekly for a period of 3 months. 4. Inappropriate influence of weight and shape on appraisal of oneself. (Based on APA, 2013.) Rita was a 26-year-old manager of a local Italian restaurant and lived in the same city as her parents. Her childhood was not a happy one. Her parents divorced when she was about 5 years of age. She and her three older brothers remained with their mother, who often seemed overwhelmed with her situation and unable to run the household effectively. Rita would often refer to her childhood as utterly chaotic, as if no one were in charge. Within a 12-month period, 1 percent to 1.5 percent of individuals will meet the diagnostic criteria for bulimia nervosa; at least 90 percent of cases occur in females (APA, 2013). She nevertheless muddled through. When her brothers were finally all off to college or beyond, Rita entered high school, and the household seemed more manageable. Ultimately, she developed a close relationship with her mother, indeed too close, Rita suspected. Her mother seemed like her closest friend, at times the entire focus of her social life. They were both women alone, so to speak, and relied heavily on one another for comfort and support, preventing Rita from developing serious friendships. The two often went shopping together. Rita would give her mother an update on the most recent fashion trends, and her mother would talk to Rita about “how important it is to look good and be put together in this day and age.” Rita didn’t mind the advice, but sometimes she did wonder if her mother kept saying that as a way of telling her that she didn’t think she looked good. Rita later attended a local public college, majoring in business. However, she quit after 3 years to take a job at the restaurant. She had begun working in the restaurant part-time while a sophomore and after 2 years was offered the position of daytime manager. It was a well-paying job, and since her interest was business anyway, Rita figured it made sense to seize an attractive business opportunity. Her mother was not very supportive of her decision to leave college, but Rita reassured her that she intended to go back and finish up after she had worked for a while and saved some money. Just before leaving college, Rita began a serious relationship with a man whom she met at school. Their interest in each other grew, and they eventually got engaged. Everything seemed to be going well when out of the blue, her fiancé’s mental state began to deteriorate. Ultimately he manifested a pattern of schizophrenia and had to be hospitalized. As his impairment extended from days to months and then to more than a year, Rita finally had to end the engagement; she had to pick up the pieces and go on without him. She felt .
Case 9 Bulimia Nervosa in Gorenstein and Comer (2014)Rita was a.docxannandleola
Rita is a 26-year-old woman who struggles with bulimia nervosa. She engages in binge eating episodes 2-3 times per week, consuming over 4,000 calories in a single sitting. After binges, she purges through vomiting to avoid weight gain. Rita is preoccupied with her weight and body image. Though her weight is in the normal range, she is highly critical of her body and engages in frequent weighing, clothing comparisons, and mirror checking. Her disordered eating patterns have become more severe over time, further compromising her physical and mental health.
Case 8.1 Pros and Cons of Balkan Intervention59Must the a.docxannandleola
Case 8.1 Pros and Cons of Balkan Intervention59
“Must the agony of Bosnia-Herzegovina be regarded, with whatever regrets, as somebody else’s trouble?
We don’t think so, but the arguments on behalf of that view deserve an answer. Among them are the
following:
The Balkan conflict is a civil war and unlikely to spread beyond the borders of the former
Yugoslavia. Wrong. Belgrade has missiles trained on Vienna. Tito’s Yugoslavia claimed, by way of
Macedonia, that northern Greece as far south as Thessaloniki belonged under its sovereignty. Those
claims may return. ‘Civil’ war pitting non-Slavic Albanians against Serbs could spread to Albania,
Turkey, Bulgaria, and Greece.
The United States has no strategic interest in the Balkans. Wrong. No peace, no peace dividend.
Unless the West can impose the view that ethnic purity can no longer be the basis for national
sovereignty, then endless national wars will replace the Cold War. This threat has appeared in
genocidal form in Bosnia. If it cannot be contained here, it will erupt elsewhere, and the Clinton
administration’s domestic agenda will be an early casualty.
If the West intervenes on behalf of the Bosnians, the Russians will do so on behalf of the Serbs, and
the Cold War will be reborn. Wrong. The Russians have more to fear from ‘ethnic cleansing’ than
any people on Earth. Nothing would reassure them better than a new, post-Cold War Western
policy of massive, early response against the persecution of national minorities, including the
Russian minorities found in every post-Soviet republic. The Russian right may favor the Serbs, but
Russian self-interest lies elsewhere.
The Serbs also have their grievances. Wrong. They do, but their way of responding to these
grievances, according to the State Department’s annual human rights report, issued this past week,
‘dwarfs anything seen in Europe since Nazi times.’ Via the Genocide Convention, armed
intervention is legal as well as justified.
The UN peace plan is the only alternative. Wrong. Incredibly, the plan proposes the reorganization
of Bosnia-Herzegovina followed by a cease-fire. A better first step would be a UN declaration that
any nation or ethnic group proceeding to statehood on the principle of ethnic purity is an outlaw
state and will be treated as such. As now drafted, the UN peace plan, with a map of provinces that
not one party to the conflict accepts, is really a plan for continued ‘ethnic cleansing.’”
Case 8.2 Images, Arguments, and the Second Persian Gulf Crisis, 1990–
1991
The analysis of policy arguments can be employed to investigate the ways that policymakers represent or
structure problems (Chapter 3). We can thereby identify the images, or problem representations, that
shape processes of making and justifying decisions. For example, during times of crisis, the images which
United States policymakers have of another country affect deliberations about the use of peacekeeping
and negotiation, the imposition of economic sanctions, o.
Case 6-2 Not Getting Face Time at Facebook—and Getting the Last La.docxannandleola
Case 6-2 Not Getting Face Time at Facebook—and Getting the Last Laugh!
In August 2009, Facebook turned down job applicant Brian Acton, an experienced engineer who had previously worked at Yahoo and Apple. More than 4 years later, Facebook paid him $3 billion to acquire his 20% stake of WhatsApp, a start-up he had cofounded immediately after Facebook rejected his job application.(1) WhatsApp Messenger is a proprietary, cross-platform, instant-messaging subscription service for smartphones and selected feature phones that use the Internet for communication. In addition to text messaging, users can send each other images, video, and audio media messages, as well as their location using integrated mapping features.(2) How could Facebook, a highly successful firm, have made such a drastic mistake?
Back in 2009, Brian Acton was a software engineer who was out of work for what seemed like a very long time. He believed he had what it took to make a difference in the industry, but his career did not work out as planned. Even though he spent years at Apple and Yahoo, he got rejected many times by Twitter and Facebook.(3) Acton described the details of the interview process that he failed to do well in as follows:
First of all, interviewing a person for a job that requires technical skills is difficult for both the interviewer and the interviewee. Facebook is a highly desirable firm to work for and requires the best skills and talents from all of their potential employees. It is therefore not surprising that the selection process rivals, if not tops, any company in the industry. The process starts with an email or a phone call from a recruiter in response to an online application or [to] a recommendation from a friend who may work for Facebook. Sometimes, in the initial chat online, timed software coding challenges are set to find the best performers. If this chat goes well, an applicant will go on to the next level—an initial in-person interview or phone screening.(4)
In this next hurdle, the applicant will have a 45-minute chat with a fellow engineer/potential coworker, [with] whom he or she shares the same area of expertise. They will tell you about their job and what their role is in Facebook; then they ask about the applicant’s résumé, motivation, and interests. Additionally, the applicant will be tested about his or her technical skills, coding exercises, and programming abilities.(5)
If successful, the applicant will be invited for back-to-back interviews. This part of the process is very grueling and stressful since all the interviews take place throughout a single day. The candidate will also be asked to manually write a program on a whiteboard to make sure that the applicant is knowledgeable about program writing. The goal in this final step is to see how one approaches a problem and comes up with a solution [that] is simple enough to solve in 10–30 minutes and can be easily explained.(6)
As a potential coworker, the applicant will be te.
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CASE 6B – CHESTER & WAYNE Chester & Wayne is a regional .docxannandleola
CASE 6B – CHESTER & WAYNE
Chester & Wayne is a regional food distribution company. Mr. Chester, CEO, has asked your
assistance in preparing cash-flow information for the last three months of this year. Selected
accounts from an interim balance sheet dated September 30, have the following balances:
Cash $142,100 Accounts payable $354,155
Marketable securities 200,000 Other payables 53,200
Accounts receivable $1,012,500
Inventories 150,388
Mr. Wayne, CFO, provides you with the following information based on experience and
management policy. All sales are credit sales and are billed the last day of the month of sale.
Customers paying within 10 days of the billing date may take a 2 percent cash discount. Forty
percent of the sales is paid within the discount period in the month following billing. An
additional 25 percent pays in the same month but does not receive the cash discount. Thirty
percent is collected in the second month after billing; the remainder is uncollectible. Additional
cash of $24,000 is expected in October from renting unused warehouse space.
Sixty percent of all purchases, selling and administrative expenses, and advertising expenses is
paid in the month incurred. The remainder is paid in the following month. Ending inventory is
set at 25 percent of the next month's budgeted cost of goods sold. The company's gross profit
averages 30 percent of sales for the month. Selling and administrative expenses follow the
formula of 5 percent of the current month's sales plus $75,000, which includes depreciation of
$5,000. Advertising expenses are budgeted at 3 percent of sales.
Actual and budgeted sales information is as follows:
Actual: Budgeted:
August $750,000 October $826,800
September 787,500 November 868,200
December 911,600
January 930,000
The company will acquire equipment costing $250,000 cash in November. Dividends of $45,000
will be paid in December.
The company would like to maintain a minimum cash balance at the end of each month of
$120,000. Any excess amounts go first to repayment of short-term borrowings and then to
investment in marketable securities. When cash is needed to reach the minimum balance, the
company policy is to sell marketable securities before borrowing.
The company will acquire equipment costing $250,000 cash in November. Dividends of $45,000
will be paid in December.
The company would like to maintain a minimum cash balance at the end of each month of
$120,000. Any excess amounts go first to repayment of short-term borrowings and then to
investment in marketable securities. When cash is needed to reach the minimum balance, the
company policy is to sell marketable securities before borrowing.
Questions (use of spreadsheet software is recommended):
1. Prepare a cash budget for each month of the fourth quarter and for the quarter in total.
Prepare supporting schedules as needed. (Round all budge.
CASE 9 Bulimia Nervosa Table 9-1 Dx Checklist Bulimia Nervos.docxannandleola
"CASE 9 Bulimia Nervosa Table 9-1 Dx Checklist Bulimia Nervosa 1. Repeated binge-eating episodes. 2. Repeated performance of ill-advised compensatory behaviors (e.g., forced vomiting) to prevent weight gain. 3. Symptoms take place at least weekly for a period of 3 months. 4. Inappropriate influence of weight and shape on appraisal of oneself. (Based on APA, 2013.) Rita was a 26-year-old manager of a local Italian restaurant and lived in the same city as her parents. Her childhood was not a happy one. Her parents divorced when she was about 5 years of age. She and her three older brothers remained with their mother, who often seemed overwhelmed with her situation and unable to run the household effectively. Rita would often refer to her childhood as utterly chaotic, as if no one were in charge. Within a 12-month period, 1 percent to 1.5 percent of individuals will meet the diagnostic criteria for bulimia nervosa; at least 90 percent of cases occur in females (APA, 2013). She nevertheless muddled through. When her brothers were finally all off to college or beyond, Rita entered high school, and the household seemed more manageable. Ultimately, she developed a close relationship with her mother, indeed too close, Rita suspected. Her mother seemed like her closest friend, at times the entire focus of her social life. They were both women alone, so to speak, and relied heavily on one another for comfort and support, preventing Rita from developing serious friendships. The two often went shopping together. Rita would give her mother an update on the most recent fashion trends, and her mother would talk to Rita about “how important it is to look good and be put together in this day and age.” Rita didn’t mind the advice, but sometimes she did wonder if her mother kept saying that as a way of telling her that she didn’t think she looked good. Rita later attended a local public college, majoring in business. However, she quit after 3 years to take a job at the restaurant. She had begun working in the restaurant part-time while a sophomore and after 2 years was offered the position of daytime manager. It was a well-paying job, and since her interest was business anyway, Rita figured it made sense to seize an attractive business opportunity. Her mother was not very supportive of her decision to leave college, but Rita reassured her that she intended to go back and finish up after she had worked for a while and saved some money. Just before leaving college, Rita began a serious relationship with a man whom she met at school. Their interest in each other grew, and they eventually got engaged. Everything seemed to be going well when out of the blue, her fiancé’s mental state began to deteriorate. Ultimately he manifested a pattern of schizophrenia and had to be hospitalized. As his impairment extended from days to months and then to more than a year, Rita finally had to end the engagement; she had to pick up the pieces and go on without him. She felt .
Case 9 Bulimia Nervosa in Gorenstein and Comer (2014)Rita was a.docxannandleola
Rita is a 26-year-old woman who struggles with bulimia nervosa. She engages in binge eating episodes 2-3 times per week, consuming over 4,000 calories in a single sitting. After binges, she purges through vomiting to avoid weight gain. Rita is preoccupied with her weight and body image. Though her weight is in the normal range, she is highly critical of her body and engages in frequent weighing, clothing comparisons, and mirror checking. Her disordered eating patterns have become more severe over time, further compromising her physical and mental health.
Case 8.1 Pros and Cons of Balkan Intervention59Must the a.docxannandleola
Case 8.1 Pros and Cons of Balkan Intervention59
“Must the agony of Bosnia-Herzegovina be regarded, with whatever regrets, as somebody else’s trouble?
We don’t think so, but the arguments on behalf of that view deserve an answer. Among them are the
following:
The Balkan conflict is a civil war and unlikely to spread beyond the borders of the former
Yugoslavia. Wrong. Belgrade has missiles trained on Vienna. Tito’s Yugoslavia claimed, by way of
Macedonia, that northern Greece as far south as Thessaloniki belonged under its sovereignty. Those
claims may return. ‘Civil’ war pitting non-Slavic Albanians against Serbs could spread to Albania,
Turkey, Bulgaria, and Greece.
The United States has no strategic interest in the Balkans. Wrong. No peace, no peace dividend.
Unless the West can impose the view that ethnic purity can no longer be the basis for national
sovereignty, then endless national wars will replace the Cold War. This threat has appeared in
genocidal form in Bosnia. If it cannot be contained here, it will erupt elsewhere, and the Clinton
administration’s domestic agenda will be an early casualty.
If the West intervenes on behalf of the Bosnians, the Russians will do so on behalf of the Serbs, and
the Cold War will be reborn. Wrong. The Russians have more to fear from ‘ethnic cleansing’ than
any people on Earth. Nothing would reassure them better than a new, post-Cold War Western
policy of massive, early response against the persecution of national minorities, including the
Russian minorities found in every post-Soviet republic. The Russian right may favor the Serbs, but
Russian self-interest lies elsewhere.
The Serbs also have their grievances. Wrong. They do, but their way of responding to these
grievances, according to the State Department’s annual human rights report, issued this past week,
‘dwarfs anything seen in Europe since Nazi times.’ Via the Genocide Convention, armed
intervention is legal as well as justified.
The UN peace plan is the only alternative. Wrong. Incredibly, the plan proposes the reorganization
of Bosnia-Herzegovina followed by a cease-fire. A better first step would be a UN declaration that
any nation or ethnic group proceeding to statehood on the principle of ethnic purity is an outlaw
state and will be treated as such. As now drafted, the UN peace plan, with a map of provinces that
not one party to the conflict accepts, is really a plan for continued ‘ethnic cleansing.’”
Case 8.2 Images, Arguments, and the Second Persian Gulf Crisis, 1990–
1991
The analysis of policy arguments can be employed to investigate the ways that policymakers represent or
structure problems (Chapter 3). We can thereby identify the images, or problem representations, that
shape processes of making and justifying decisions. For example, during times of crisis, the images which
United States policymakers have of another country affect deliberations about the use of peacekeeping
and negotiation, the imposition of economic sanctions, o.
Case 6-2 Not Getting Face Time at Facebook—and Getting the Last La.docxannandleola
Case 6-2 Not Getting Face Time at Facebook—and Getting the Last Laugh!
In August 2009, Facebook turned down job applicant Brian Acton, an experienced engineer who had previously worked at Yahoo and Apple. More than 4 years later, Facebook paid him $3 billion to acquire his 20% stake of WhatsApp, a start-up he had cofounded immediately after Facebook rejected his job application.(1) WhatsApp Messenger is a proprietary, cross-platform, instant-messaging subscription service for smartphones and selected feature phones that use the Internet for communication. In addition to text messaging, users can send each other images, video, and audio media messages, as well as their location using integrated mapping features.(2) How could Facebook, a highly successful firm, have made such a drastic mistake?
Back in 2009, Brian Acton was a software engineer who was out of work for what seemed like a very long time. He believed he had what it took to make a difference in the industry, but his career did not work out as planned. Even though he spent years at Apple and Yahoo, he got rejected many times by Twitter and Facebook.(3) Acton described the details of the interview process that he failed to do well in as follows:
First of all, interviewing a person for a job that requires technical skills is difficult for both the interviewer and the interviewee. Facebook is a highly desirable firm to work for and requires the best skills and talents from all of their potential employees. It is therefore not surprising that the selection process rivals, if not tops, any company in the industry. The process starts with an email or a phone call from a recruiter in response to an online application or [to] a recommendation from a friend who may work for Facebook. Sometimes, in the initial chat online, timed software coding challenges are set to find the best performers. If this chat goes well, an applicant will go on to the next level—an initial in-person interview or phone screening.(4)
In this next hurdle, the applicant will have a 45-minute chat with a fellow engineer/potential coworker, [with] whom he or she shares the same area of expertise. They will tell you about their job and what their role is in Facebook; then they ask about the applicant’s résumé, motivation, and interests. Additionally, the applicant will be tested about his or her technical skills, coding exercises, and programming abilities.(5)
If successful, the applicant will be invited for back-to-back interviews. This part of the process is very grueling and stressful since all the interviews take place throughout a single day. The candidate will also be asked to manually write a program on a whiteboard to make sure that the applicant is knowledgeable about program writing. The goal in this final step is to see how one approaches a problem and comes up with a solution [that] is simple enough to solve in 10–30 minutes and can be easily explained.(6)
As a potential coworker, the applicant will be te.
Case 6.4 The Case of the Poorly Performing SalespersonEd Markham.docxannandleola
Case 6.4 The Case of the Poorly Performing Salesperson
Ed Markham, the African American sales manager at WCTV, is considering how to handle a problem with one of his salespersons, Jane Folsom, who is White. Ed was promoted to sales manager three months ago after working at WCTV for 2 years. He earned his promotion by exceeding sales goals every month after his first on the job. He developed a research report using secondary data like MRI and the Lifestyle Market Analyst to analyze the market. His former boss praised the report, gave a copy to all salespersons, and included a summary of it in the rate card. When his former boss left for a new job in a larger market, he recommended Ed as his replacement.
Jane has been a salesperson at WCTV for 2 years. For most of that time, she has exceeded sales quotas about as much as Ed had. For the past 3 months, she has not met sales quotas. After his second month as sales manager, Ed talked to Jane about her performance. She attributed her below-average performance to the closing of a major advertiser, Anthony’s Fashions. This local clothing store closed because several major retailers, including JC Penney and Dillard’s, had opened at the local mall.
Ed listened to Jane’s explanation and then suggested ways to obtain new clients. He asked Jane whether she had set personal sales goals, set up a prospect file of new and inactive advertisers as well as existing businesses that were potential clients, come up with research and data on the market to use in presentations and reports to clients, come up with new ideas or opportunities to advertise for clients, or asked her clients about their needs and goals (Shaver, 1995). Jane said no, she simply telephoned or visited her clients regularly to see if they wanted to run ads.
Ed also asked Jane why several of her clients had not paid their bills. He explained that a salesperson must check out a client’s ability to pay before running a schedule. Jane replied that she was not aware of that fact and that no one had ever trained her to sell. She had sold time for a radio station before, but that was all the training she had. Ed’s predecessor had just hired her and cut her loose.
Ed gave Jane a memo after their first meeting a month ago asking her to focus on sales training for the next month. First, she should read Shaver’s (1995) Making the Sale! How to Sell Media With Marketing. He gave her a copy, told her to read it, and asked her to contact him if she had any questions. After reading the book, he told her that she should establish written personal sales goals, begin to develop a prospect file (with two new and two inactive clients), and develop three ideas for new advertising opportunities for existing clients. In the memo, Ed told Jane that he would not hold her to sales performance standards that month. He wanted Jane to focus on doing the background work he assigned to help her improve her future sales performance.
At the meeting a month later, Ed discovered.
Case 5.6Kelo v City of New London545 U.S. 469 (2005)Ye.docxannandleola
Case 5.6
Kelo v City of New London
545 U.S. 469 (2005)
Yes, Actually, They Can Take That Away From You
Facts
In 1978, the city of New London, Connecticut, undertook a redevelopment plan for purposes of creating a redeveloped area in and around the existing park at Fort Trumbull. The plan sought to develop the related ambience a state park should have, including the absence of pink cottages and other architecturally eclectic homes. Part of the redevelopment plan was the city’s deal with Pfizer Corporation for the location of its research facility in the area. The preface to the city’s development plan included the following statement of goals and purpose:
To create a development that would complement the facility that Pfizer was planning to build, create jobs, increase tax and other revenues, encourage public access to and use of the city’s waterfront, and eventually “build momentum” for the revitalization of the rest of the city, including its downtown area.
The affected property owners, including Susette Kelo, live in homes and cottages (15 total) located in and around other existing structures that would be permitted to stay in the area designated for the proposed new structures (under the city’s economic development plan) that would be placed there primarily by private land developers and corporations. The city was assisted by a private, nonprofit corporation, the New London Development Corporation (NLDC), in the development of the economic plan and piloting it through the various governmental processes, including that of city council approval. The central focus of the plan was getting Pfizer to the Fort Trumbull area (where the homeowners and their properties were located) with the hope of a resulting economic boost that such a major corporate employer can bring to an area.
Kelo and the other landowners whose homes would be razed to make room for Pfizer and the accompanying and resulting economic development plan filed suit challenging New London’s legal authority to take their homes. The trial court issued an injunction preventing New London from taking certain of the properties but allowing others to be taken. The appellate court found for New London on all the claims, and the landowners (petitioners) appealed.
Judicial Opinion
STEVENS, Justice Two polar propositions are perfectly clear. On the one hand, it has long been accepted that the sovereign may not take the property of A for the sole purpose of transferring it to another private party B, even though A is paid just compensation. On the other hand, it is equally clear that a State may transfer property from one private party to another if future “use by the public” is the purpose of the taking; the condemnation of land for a railroad with common-carrier duties is a familiar example. Neither of these propositions, however, determines the disposition of this case.
The disposition of this case therefore turns on the question whether the City’s development plan serves a “public purpos.
CASE 5.10 FIBREBOARD PAPER PRODUCTS CORP. V. NLRB SUPREME COURT OF.docxannandleola
CASE 5.10 FIBREBOARD PAPER PRODUCTS CORP. V. NLRB SUPREME COURT OF THE UNITED STATES, 379 U.S. 203 (1964).
[After receiving union proposals for contract revisions for the benefit of the maintenance workers at the company’s Emeryville, California, plant, the company advised the union that negotiations for a new contract would be pointless because it had definitely decided to contract out the work performed by the employees covered by the agreement upon the expiration of the agreement. The company planned to replace these employees with an independent contractor’s employees and expected that substantial savings would be effected by this contracting-out of the work. The Board ordered the company to reinstate the maintenance operation with the union employees, reinstate the employees with back pay, and fulfill its statutory bargaining obligation. The court of appeals granted the Board’s enforcement petition, and the Supreme Court agreed to hear the case.]
WARREN, C. J.... I. Section 8(a)(5) of the National Labor Relations Act provides that it shall be an unfair labor practice for an employer “to refuse to bargain collectively with the representatives of his employees.” Collective bar- gaining is defined in Section 8(d)
as the performance of the mutual obligation of the employer and the representative of the employees to meet at reasonable times and confer in good faith with respect to wages, hours, and other terms and conditions of employment.
“Read together, these provisions establish the obligation of the employer and the representative of its employees to bargain with each other in good faith with respect to ‘wages, hours, and other terms and conditions of employment....’ The duty is limited to those subjects, and within that area neither is legally obligated to yield. Labor Board v. American Ins. Co., 343 U.S. 395. As to other matters, however, each party is free to bargain or not to bargain....” Labor Board v. Wooster Div. of Borg-Warner Corp., 356 U.S. 342, 349. Because of the limited grant of certiorari, we are concerned here only with whether the subject upon which the employer allegedly refused to bargain— contracting out of plant maintenance work previously performed by employees in the bargaining unit, which the employees were capable of continuing to perform—is covered by the phrase “terms and conditions of employment” within the meaning of Section 8(d).
The subject matter of the present dispute is well within the literal meaning of the phrase “terms and conditions of employment.”
As the Court of Appeals pointed out, it is not necessary that it be likely or probable that the union will yield or supply a feasible solution but rather that the union be afforded an opportunity to meet management’s legitimate complaints that its maintenance was unduly costly.
We are thus not expanding the scope of mandatory bargaining to hold, as we do now, that the type of “contracting out” involved in this case—the replacement of employees in the exi.
Case 4 The McDonald’s China Food Supplier Scandal1. What we.docxannandleola
Case 4:
The McDonald’s China Food Supplier Scandal
1. What were the root causes for Husi’s misbehavior?
2. What are the major challenges faced by the multinationals such as McDonald’s in supply chain management in China?
3. Should McDonald’s be held responsible for the scandal? How could McDonald’s avoid similar situations from happening again?
4. Should OSI be held responsible for the scandal? What should OSI do to prevent similar situations from happening again?
.
Case 3 Neesha Wilson Phoenix Rising Risks, Protective Factors, and.docxannandleola
Neesha Wilson, a 10-year-old African American girl, was referred for assessment by her school due to poor academic performance and behavioral issues. She lives with her mother and older brother, as her father left the family 3 years ago. Testing showed Neesha's intellectual abilities were likely underestimated and her academic skills were well above grade level, though she was repeating 4th grade. Neesha reported worries about school performance and family stressors, and showed signs of anxiety through somatic symptoms like fatigue. While most scores were normal, elevated scales indicated concerns with negative mood, physiological arousal, and somatic complaints.
Case 48 Sun Microsystems Done by Nour Abdulaziz Maryam .docxannandleola
Case 48: Sun Microsystems
Done by: Nour Abdulaziz
Maryam Barifah
Shrouq Al-Jaadi
Balqees Mekhalfi
Yara El-Feki
Introduction
•In 2009, Oracle was planning to acquire Sun Microsystems.
•This acquisition would allow Oracle;
•to further diversify their brand, customers and acquire various new platforms that would be added to their portfolio such as MySQL, Solaris and Java.
•Oracle originally placed an offer of $9.50 per share price which is considerably higher than Sun Microsystem’s price that is $6.69.
•This will cut the production costs and make the company more efficient throughout all the value chain.
•Oracle aimed to capitalize on Sun Microsystem’s decline by getting particular assets or the whole company at the deflated price.
Is Sun Microsystems a good strategic fit for Oracle? Should Oracle acquire Sun Microsystems?
- as it will allow them to achieve their vision of becoming the Apple of the software industry.
- it will allow the company to deliver high-quality customer products by combining both hardware and software components, hence reducing the consumer setup process.
Continue
It will provide Oracle with the needed expansion.
-This acquisition fits Oracle’s overall strategy which is to improve through acquiring and effectively integrating other companies
Worth of Sun Microsystems and Valuation Approaches
To know how much Sun Microsystems worth, we must find the Stand Alone Value of the company.
The Stand Alone value represents the present value of Sun Microsystem individually before factoring the synergy that would be created when Oracle acquires Sun.
Another method is the value of Sun Microsystem with synergies, which after being acquired by Oracle, must be found. This is done to see whether or not the acquisition was a proper strategic decision or not
Another method of valuing the Sun Microsystem is through the comparative company analysis (CCA). That is done through the thorough assessment of rival and peer businesses of similar size and industry.
Finally, the acquisition price, which is the price that is paid to the target when it is first acquired, is also used as a separate method of valuation. The value of the acquisition price ranges between the values of the stand-alone and the synergies.
USING THE DCF
To be able to find the values of both, the Stand Alone and the synergies, we have decided the best way to do so is by calculating the discounted cash flow (DCF) by using the multiples and the perpetuity growth methods and finding the average of both.
DCF Using Multiples MethodDCF Using Perpetuity Growth MethodIt does not consider long-term growth rate or the economics of business.This method seems inaccurate as the company assumes a certain growth rate will remains the same 2014 onwards (forever) which is unrealistic.It is considered a challenging method to use as it is very difficult to identify truly comparable companies.
USING THE WACC
The weig.
CASE 42 Myasthenia Gravis The immune response turns agai.docxannandleola
CASE 42 Myasthenia Gravis
The immune response turns against the host.
The specific adaptive immune response can, in rare instances, be mounted
against self antigens and cause autoimmune disease. Injury to body tissues
can result from antibodies directed against cell-surface or extracellular-matrix
molecules, from antibodies bound to circulating molecules that deposit as
immune complexes, or from clones of T cells that react with self antigens. A
special class of autoimmune disease is caused by autoantibodies against cell
surface receptors (Fig. 42.1). Graves' disease and myasthenia gravis are two
well-studied examples . Graves' disease is caused by autoantibodies against
the receptor on thyroid cells for thyroid-stimulating hormone (TSH), secreted
by the pituitary gland. In this disease, autoantibody binds to the TSH recep
tor; like TSH, it stimulates the thyroid gland to produce thyroid hormones.
In myasthenia gravis, the opposite effect is observed: antibodies against the
acetylcholine receptor at the neuromuscular junction impede the binding of
acetylcholine and stimulate internalization of the receptor, thereby block
ing the t ransmission of nerve impulses by acetylcholine (Fig. 42.2). In addi
tion, the presence of autoantibodies at the neuromuscular junction initiates
complement-mediated lysis ofthe muscle endplate and damages the muscle
membrane.
Myasthenia gravis means severe (gravis) muscle (my) weakness (asthenia).
This disease was first identified as an autoimmune disease when an immun
ologist immunized rabbits with purified acetylcholine receptors to obtain
antibodies against this receptor. He noticed that the rabbits developed floppy
ears, like the droopy eyelids (ptosis) that are the most characteristic symptom
of myasthenia gravis in humans. Subsequently, patients with this disease
were found to have antibodies against the acetycholine receptor. In addition,
pregnant women with myasthenia gravis transfer the disease to their newborn
infants. As IgG is the only maternal serum protein that crosses the placenta
fro m mother to fetus, neonatal myasthenia gravis is clear evidence that
myasthenia gravis is caused by an anti-IgG antibody. More recently, patients
with myasthenia gravis have been identified who have autoantibodies against
muscle-specific kinase (MUSK) rather than the acetylcholine receptor.
MUSK is a tyrosine kinase receptor involved in clustering acetylcholine
receptors; therefore, these autoantibodies also inhibit signaling through the
neuromuscular junction.
Topics bearing on
this case:
Humoral autoimmunity
Transfer of maternal
antibodies
Mechanisms for
breaking tolerance
This case was prepared by RaifGeha , MD, in collaboration with Janet Chou, MD.
~ Case 42: Myasthenia Gravis
Fig. 42.1 Autoimmune diseases caused
by antibody against surface or matrix
antigens. These are known as type II
autoimmune diseases. Damage by
IgE-mediated responses (type I) does no.
Case 4 JetBlue Delighting Customers Through Happy JettingIn the.docxannandleola
Case 4 JetBlue: Delighting Customers Through Happy Jetting
In the early years, JetBlue was a thriving young airline with a strong reputation for outstanding service. In fact, the low-fare airline referred to itself as a customer service company that just happened to fly planes. But on a Valentine’s Day, JetBlue was hit by the perfect storm, literally, of events that led to an operational meltdown. One of the most severe storms of the decade covered JetBlue’s main hub at New York’s John F. Kennedy International Airport with a thick layer of snow and ice. JetBlue did not have the infrastructure to deal with such a crisis. The severity of the storm, coupled with a series of poor management decisions, left JetBlue passengers stranded in planes on the runway for up to 11 hours. Worse still, the ripple effect of the storm created major JetBlue flight disruptions for six more days. Understandably, customers were livid. JetBlue’s efforts to clean up the mess following the six-day Valentine’s Day nightmare cost over $30 million in overtime, flight refunds, vouchers for future travel, and other expenses. But the blow to the company’s previously stellar customer-service reputation stung far more than the financial fallout. JetBlue became the butt of jokes by late night talk show hosts. Some industry observers even predicted that this would be the end
of JetBlue. But just three years later, the company is not only still flying, it is growing, profitable, and hotter than ever. During a serious economic downturn competing airlines were cut routes, retiring aircraft, laying off employees, and lost money. JetBlue added planes, expanded into new cities, hired thousands of new employees, and turning profits.
Truly Customer Focused What’s the secret to JetBlue’s success? Quite simply, it’s an obsession with making sure that every customer experience lives up to the company slogan, “Happy Jetting.” Lots of companies say they focus on customers. But at JetBlue, customer well-being is ingrained in the culture. From the beginning, JetBlue set out to provide features that would delight customers. For example, most air travelers expect to be squashed when flying coach. But JetBlue has configured its seats with three more inches of legroom than the average airline seat. That may not sound like much. But those three inches allow six-foot three-inch Arianne Cohen, author of The Tall Book: A Celebration of Life from on High, to stretch out and even cross her legs. If that’s not enough, for as little as $10 per flight, travelers can reserve one of JetBlue’s “Even More Legroom” seats, which offer even more space and a flatter recline position. Add the fact that every JetBlue seat is well padded and covered in leather, and you already have an air travel experience that rivals first-class accommodations (something JetBlue doesn’t offer). Food and beverage is another perk that JetBlue customers enjoy. The airline doesn’t serve meals, but it offers the best selection of free.
Case 4-2 Hardee TransportationThe Assignment Answer the four .docxannandleola
Case 4-2 Hardee Transportation
The Assignment: Answer the four (4) questions at the end of Case 4-2
Resources: Course Textbook, Appendix 4B, Table 4B-1, Attached worksheet (Word or Excel format)
Acceptable Length:
Show your work for solution to questions 1 and 2
. Well-written responses to question 3 and 4.
Formatting Requirements:
Enter your name and date
Provide well-structured solutions/answers- incomplete answers will receive partial credit
Show your work
2. Answer case questions,
using the attached word template or excel document
. Complete assignment and submit as an attachment using the assignment link when finished.
.
Case 3-8 Accountant takes on Halliburton and Wins!1. Descri.docxannandleola
Case 3-8 Accountant takes on Halliburton and Wins!
1. Describe the inadequacies in the corporate governance system at Halliburton.
2. Consider the role of KPMG in the case with respect to the accounting and auditing issues. How did the firms’ actions relate to the ethical and professional expectations for CPAs by the accounting profession?
3. The Halliburton case took place before the Dodd-Frank Financial Reform Act was adopted by Congress. Assume Dodd-Frank had been in effect and Menendez decided to inform the SEC under Dodd-Frank rather than SOX because it had been more than 180 days since the accounting violation had occurred. Given the facts of the case would Menendez have qualified for whistleblower protection? Explain.
4. Some critics claim that while Menendez’s actions may have been courageous, he harmed others along the way. His family was in limbo for many years and had to deal with the agony of being labeled a whistleblower and disloyal to Halliburton. The company’s overall revenue did not change; a small amount was merely shifted to an earlier period. Halliburton didn't steal any money, they didn't cheat the IRS, they didn't cheat their customers or their employees. In fact, they lessened their cash flows by paying out taxes earlier than they should have under the rules. How do you respond to these criticisms?
.
Case 3 Ford’s Pinto Fires The Retrospective View of Ford’s Fiel.docxannandleola
Case 3
Ford’s Pinto Fires: The Retrospective View of Ford’s Field Recall Coordinator
Brief Overview of the Ford Pinto Fires
Determined to compete with fuel- efficient Volkswagen and Japanese imports, the Ford Motor Company introduced the subcompact Pinto in the 1971 model year. Lee Iacocca, Ford’s president at the time, insisted that the Pinto weigh no more than 2,000 pounds and cost no more than $2,000. Even with these restrictions, the Pinto met federal safety standards, although some people have argued that strict adherence to the restrictions led Ford engineers to compromise safety. Some 2 million units were sold during the 10- year life of the Pinto.
The Pinto’s major design flaw— a fuel tank prone to rupturing with moderate speed rear- end collisions— surfaced not too long after the Pinto’s entrance to the market. In April 1974, the Center for Auto Safety petitioned the National Highway Traffic Safety Administration (NHTSA) to recall Ford Pintos due to the fuel tank design defect. The Center for Auto Safety’s petition was based on reports from attorneys of three deaths and four serious injuries in moderate- speed rear- end collisions involving Pintos. The NHTSA did not act on this petition until 1977. As a result of tests performed for the NHTSA, as well as the extraordinary amount of publicity generated by the problem, Ford agreed, on June 9, 1978, to recall 1.5 million 1971– 1976 Ford Pintos and 30,000 1975– 1976 Mercury Bobcat sedan and hatchback models for modifications to the fuel tank. Recall notices were mailed to the affected Pinto and Bobcat owners in September 1978. Repair parts were to be delivered to all dealers by September 15, 1978.
Unfortunately, the recall was initiated too late for six people. Between June 9 and September 15, 1978, six people died in Pinto fires after a rear impact. Three of these people were teenage girls killed in Indiana in August 1978 when their 1973 Pinto burst into flames after being rear- ended by a van. The fiery deaths of the Indiana teenagers led to criminal prosecution of the Ford Motor Company on charges of reckless homicide, marking the first time that an American corporation
was prosecuted on criminal charges. In the trial, which commenced on January 15, 1980, “Indiana state prosecutors alleged that Ford knew Pinto gasoline tanks were prone to catch fire during rear- end collisions but failed to warn the public or fix the problem out of concern for profits.” On March 13, 1980, a jury found Ford innocent of the charges. Production of the Pinto was discontinued in the fall of 1980.
Enter Ford’s Field Recall Coordinator
Dennis A. Gioia, currently a professor in the Department of Management and Organization at Pennsylvania State University, was the field recall coordinator at Ford Motor Company as the Pinto fuel tank defect began unfolding. Gioia’s responsibilities included the operational coordination of all the current recall
92 Business Ethics
campaigns, tracking incoming information.
Case 3Competition in the Craft Brewing Industry in 2017John D. Var.docxannandleola
Case 3Competition in the Craft Brewing Industry in 2017
John D. Varlaro
Johnson & Wales University
John E. Gamble
Texas A&M University–Corpus Christi
Locally produced or regional craft beers caused a seismic shift in the U.S. beer industry during the early 2010s with the gains of the small, regional newcomers coming at the expense of such well-known brands as Budweiser, Miller, Coors, and Bud Light. Craft breweries, which by definition sold fewer than 6 million barrels (bbls) per year, expanded rapidly with the deregulation of intrastate alcohol distribution and retail laws and a change in consumer preferences toward unique and high-quality beers. The growing popularity of craft beers allowed the total beer industry in the United States to increase by 6.7 percent annually between 2011 and 2016 to reach $39.5 billion. The production of U.S. craft breweries more than doubled from 11.5 million bbls per year to about 24.6 million bbls per year during that time. In addition, production by microbreweries and brewpubs accounted for 90 percent of craft brewer growth in 2016.1
The industry had begun to show signs of a slowdown going into 2017, with Boston Beer Company, the second largest craft brewery in the United States and known for its Samuel Adams brand, experiencing a 4 percent sales decline in 2016 that erased two years of of growth. The annual revenues of Anheuser-Busch InBev SA, whose portfolio included global brands Budweiser, Corona, and Stella Artois and numerous international and local brands, remained relatively consistent from 2014 to 2016. However, the sales volume of Anheuser-Busch’s flagship brands and its newly acquired and international brands such as Corona, Goose Island, Shock Top, Beck’s, and St. Pauli Girl allowed it to control 45.8 percent of the U.S. market for beer in 2016.2
Industry competition was increasing as grain price fluctuations affected cost structures and growing consolidation within the beer industry—led most notably by AB InBev’s acquisition of several craft breweries, Grupo Modelo, and its pending $104 billion acquisition of SABMiller—created a battle for market share. While the market for specialty beer was expected to gradually plateau by 2020, it appeared that the slowing growth had arrived by 2017. Nevertheless, craft breweries and microbreweries were expected to expand in number and in terms of market share as consumers sought out new pale ales, stouts, wheat beers, pilsners, and lagers with regional or local flairs.The Beer Market
The total economic impact of the beer market was estimated to be 2.0 percent of the total U.S. GDP in 2016 when variables such as jobs within beer production, sales, and distribution were included.3Exhibit 1 presents annual beer production statistics for the United States between 2006 and 2016.
Year
Barrels Produced (in millions)*
2006
198
2007
200
2008
200
2009
197
2010
195
2011
193
2012
196
2013
192
2014
193
2015
191
2016
189
*Rounded to the nearest million. .
CASE 3.2 Ethics, Schmethics-Enrons Code of EthicsIn Jul.docxannandleola
CASE 3.2 "Ethics, Schmethics"-Enron's Code of Ethics
In July 2000, Enron Corporation published an internal code of ethics docu-
ment that ran 64 pages in length (see the Appendix 1).Page 12 of the document
proudly announced the company's position on business ethics:
Employees of Enron Corp., its subsidiaries, and its affiliated companies
(collectively the "Company") are charged with conducting their business
affairs in accordance with the highest ethical standards. An employee
shall not conduct himself or herself in a manner which directly or indi-
rectly would be detrimental to the best interests of the Company or in
a manner which would bring to the employee financial gain separately
derived as a direct consequence of his or her employment with the Com-
pany. Moral as well as legal obligations will be fulfilled openly, promptly,
and in a manner which will reflect pride on the Company's name.
Products and services of the Company will be of the highest quality and
as represented. Advertising and promotion will be truthful, not exagger-
ated or misleading.
Agreements, whether contractual or verbal, will be honored. No bribes,
bonuses, kickbacks, lavish entertainment, or gifts will be given or received
. in exchange for special position, price or privilege . . . Relations with
the Company's many publics-customers, stockholders, governments,
employees, suppliers, press, and bankers-will be conducted in honesty,
candor, and fairness." .- ~ ~ ~ -
Subsequent investigations into the inner workings of Enron Corp. revealed that
the only time this code of ethics received formal attention (other than, presum-
ably,when it was created and formally accepted) was when the board of directors
voted to waive key provisions of the code in order to allow the off-balance-sheet
partnerships that Chief Financial Officer Andy Fastow ultimately used to hide
over half a billion dollars of debt from analysts and investors.
A more realistic picture of the apparent flexibility of Enron's ethical culture
can be found in the extreme conflict of interest represented in its relationship
with Arthur Andersen. Andersen provided both consulting and auditing ser-
vices for fees running into millions of dollars-money that became so critical to
Andersen's continued growth that its employees were encouraged to sign off on
off-balance-sheet transactions-transactions that were not shown on Enron's
publicly-reported balance sheet-that stretched the limits of generally accepted
accounting principles (GAAP) to their furthest edges. In addition, Enron hired
former Andersen employees to manage the affairs of their former colleagues,
which further strengthened the conflict of interest in a relationship that was
supposed, at the very least, to be at arm's length, and, at best, above reproach.
1. What is the purpose of a code of ethics?
2. Do you think the employees of Enron Corp. were told about the vote to put
aside key elements of the code of ethics? If not, why not? If they had .
A review of the growth of the Israel Genealogy Research Association Database Collection for the last 12 months. Our collection is now passed the 3 million mark and still growing. See which archives have contributed the most. See the different types of records we have, and which years have had records added. You can also see what we have for the future.
A workshop hosted by the South African Journal of Science aimed at postgraduate students and early career researchers with little or no experience in writing and publishing journal articles.
This presentation was provided by Steph Pollock of The American Psychological Association’s Journals Program, and Damita Snow, of The American Society of Civil Engineers (ASCE), for the initial session of NISO's 2024 Training Series "DEIA in the Scholarly Landscape." Session One: 'Setting Expectations: a DEIA Primer,' was held June 6, 2024.
ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...PECB
Denis is a dynamic and results-driven Chief Information Officer (CIO) with a distinguished career spanning information systems analysis and technical project management. With a proven track record of spearheading the design and delivery of cutting-edge Information Management solutions, he has consistently elevated business operations, streamlined reporting functions, and maximized process efficiency.
Certified as an ISO/IEC 27001: Information Security Management Systems (ISMS) Lead Implementer, Data Protection Officer, and Cyber Risks Analyst, Denis brings a heightened focus on data security, privacy, and cyber resilience to every endeavor.
His expertise extends across a diverse spectrum of reporting, database, and web development applications, underpinned by an exceptional grasp of data storage and virtualization technologies. His proficiency in application testing, database administration, and data cleansing ensures seamless execution of complex projects.
What sets Denis apart is his comprehensive understanding of Business and Systems Analysis technologies, honed through involvement in all phases of the Software Development Lifecycle (SDLC). From meticulous requirements gathering to precise analysis, innovative design, rigorous development, thorough testing, and successful implementation, he has consistently delivered exceptional results.
Throughout his career, he has taken on multifaceted roles, from leading technical project management teams to owning solutions that drive operational excellence. His conscientious and proactive approach is unwavering, whether he is working independently or collaboratively within a team. His ability to connect with colleagues on a personal level underscores his commitment to fostering a harmonious and productive workplace environment.
Date: May 29, 2024
Tags: Information Security, ISO/IEC 27001, ISO/IEC 42001, Artificial Intelligence, GDPR
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Training: ISO/IEC 27001 Information Security Management System - EN | PECB
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How to Setup Warehouse & Location in Odoo 17 InventoryCeline George
In this slide, we'll explore how to set up warehouses and locations in Odoo 17 Inventory. This will help us manage our stock effectively, track inventory levels, and streamline warehouse operations.
it describes the bony anatomy including the femoral head , acetabulum, labrum . also discusses the capsule , ligaments . muscle that act on the hip joint and the range of motion are outlined. factors affecting hip joint stability and weight transmission through the joint are summarized.
LAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UPRAHUL
This Dissertation explores the particular circumstances of Mirzapur, a region located in the
core of India. Mirzapur, with its varied terrains and abundant biodiversity, offers an optimal
environment for investigating the changes in vegetation cover dynamics. Our study utilizes
advanced technologies such as GIS (Geographic Information Systems) and Remote sensing to
analyze the transformations that have taken place over the course of a decade.
The complex relationship between human activities and the environment has been the focus
of extensive research and worry. As the global community grapples with swift urbanization,
population expansion, and economic progress, the effects on natural ecosystems are becoming
more evident. A crucial element of this impact is the alteration of vegetation cover, which plays a
significant role in maintaining the ecological equilibrium of our planet.Land serves as the foundation for all human activities and provides the necessary materials for
these activities. As the most crucial natural resource, its utilization by humans results in different
'Land uses,' which are determined by both human activities and the physical characteristics of the
land.
The utilization of land is impacted by human needs and environmental factors. In countries
like India, rapid population growth and the emphasis on extensive resource exploitation can lead
to significant land degradation, adversely affecting the region's land cover.
Therefore, human intervention has significantly influenced land use patterns over many
centuries, evolving its structure over time and space. In the present era, these changes have
accelerated due to factors such as agriculture and urbanization. Information regarding land use and
cover is essential for various planning and management tasks related to the Earth's surface,
providing crucial environmental data for scientific, resource management, policy purposes, and
diverse human activities.
Accurate understanding of land use and cover is imperative for the development planning
of any area. Consequently, a wide range of professionals, including earth system scientists, land
and water managers, and urban planners, are interested in obtaining data on land use and cover
changes, conversion trends, and other related patterns. The spatial dimensions of land use and
cover support policymakers and scientists in making well-informed decisions, as alterations in
these patterns indicate shifts in economic and social conditions. Monitoring such changes with the
help of Advanced technologies like Remote Sensing and Geographic Information Systems is
crucial for coordinated efforts across different administrative levels. Advanced technologies like
Remote Sensing and Geographic Information Systems
9
Changes in vegetation cover refer to variations in the distribution, composition, and overall
structure of plant communities across different temporal and spatial scales. These changes can
occur natural.
Walmart Business+ and Spark Good for Nonprofits.pdfTechSoup
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You will hear from Liz Willett, the Head of Nonprofits, and hear about what Walmart is doing to help nonprofits, including Walmart Business and Spark Good. Walmart Business+ is a new offer for nonprofits that offers discounts and also streamlines nonprofits order and expense tracking, saving time and money.
The webinar may also give some examples on how nonprofits can best leverage Walmart Business+.
The event will cover the following::
Walmart Business + (https://business.walmart.com/plus) is a new shopping experience for nonprofits, schools, and local business customers that connects an exclusive online shopping experience to stores. Benefits include free delivery and shipping, a 'Spend Analytics” feature, special discounts, deals and tax-exempt shopping.
Special TechSoup offer for a free 180 days membership, and up to $150 in discounts on eligible orders.
Spark Good (walmart.com/sparkgood) is a charitable platform that enables nonprofits to receive donations directly from customers and associates.
Answers about how you can do more with Walmart!"
The simplified electron and muon model, Oscillating Spacetime: The Foundation...RitikBhardwaj56
Discover the Simplified Electron and Muon Model: A New Wave-Based Approach to Understanding Particles delves into a groundbreaking theory that presents electrons and muons as rotating soliton waves within oscillating spacetime. Geared towards students, researchers, and science buffs, this book breaks down complex ideas into simple explanations. It covers topics such as electron waves, temporal dynamics, and the implications of this model on particle physics. With clear illustrations and easy-to-follow explanations, readers will gain a new outlook on the universe's fundamental nature.
How to Manage Your Lost Opportunities in Odoo 17 CRMCeline George
Odoo 17 CRM allows us to track why we lose sales opportunities with "Lost Reasons." This helps analyze our sales process and identify areas for improvement. Here's how to configure lost reasons in Odoo 17 CRM
How to Manage Your Lost Opportunities in Odoo 17 CRM
MINI REVIEW ARTICLEpublished 04 March 2015doi 10.3389.docx
1. MINI REVIEW ARTICLE
published: 04 March 2015
doi: 10.3389/fnins.2015.00064
Lessons from the analysis of nonhuman primates for
understanding human aging and neurodegenerative
diseases
Jean-Michel Verdier 1,2,3*, Isabelle Acquatella 1,2,3, Corinne
Lautier 1,2,3, Gina Devau 1,2,3,
Stéphanie Trouche 1,2,3, Christelle Lasbleiz 1,2,3 and Nadine
Mestre-Francés 1,2,3
1 Université de Montpellier, Montpellier, France
2 Institut National de la Santé et de la Recherche Médicale,
U1198, Montpellier, France
3 Ecole Pratique des Hautes Etudes, Paris, France
Edited by:
Patrick Lewis, University of Reading,
UK
Reviewed by:
Ricardo Insausti, University of
Castilla -la Mancha, Spain
Varun Kesherwani, University of
Nebraska Medical Center, USA
*Correspondence:
2. Jean-Michel Verdier, University of
Montpellier, Place Eugène Bataillon,
CC105, 34095 Montpellier, France
e-mail: [email protected]
univ-montp2.fr
Animal models are necessary tools for solving the most serious
challenges facing medical
research. In aging and neurodegenerative disease studies,
rodents occupy a place of
choice. However, the most challenging questions about
longevity, the complexity and
functioning of brain networks or social intelligence can almost
only be investigated in
nonhuman primates. Beside the fact that their brain structure is
much closer to that of
humans, they develop highly complex cognitive strategies and
they are visually-oriented
like humans. For these reasons, they deserve consideration,
although their management
and care are more complicated and the related costs much
higher. Despite these caveats,
considerable scientific advances have been possible using
nonhuman primates. This
review concisely summarizes their role in the study of aging
and of the mechanisms
involved in neurodegenerative disorders associated mainly with
cognitive dysfunctions
(Alzheimer’s and prion diseases) or motor deficits (Parkinson’s
and related diseases).
Keywords: neuroscience, brain, aging, neurodegenerative
diseases, nonhuman primate
WHY DO WE NEED ANIMAL MODELS?
3. The simplest answer to this question is to increase our general
knowledge, to experimentally test theories. Animal model use-
fulness is manifold, from the study of physiological processes
to
the identification of disease-causing mechanisms. Indeed, phys-
iopathological studies are of the utmost importance for develop-
ing diagnostic and therapeutic approaches based on the
discovery
of new, more sensitive and specific biomarkers, the identifica-
tion of the mechanism of action of drugs, the establishment of
pharmacodynamics and pharmacokinetic parameters, the toxic-
ity analysis of new compounds or the assessment of clinical
drug
regimens.
Many different animal models, ranging from unicellular
organisms (bacteria, yeast) to invertebrates (the roundworm
Caenorhabditis elegans or the fruit fly Drosophila melanogaster)
and vertebrates (fish and mammals), are currently used for
research on aging and neurodegenerative disorders. They are all
of interest and importance, but they also show limitations and
drawbacks. Most studies on neurodegenerative diseases have
been
done in transgenic animals (Gama Sosa et al., 2012),
particularly
in mice. Indeed, as the production and handling of transgenic
mice is currently quite easy, they have played and continue to
play a very important role in biomedical research. Nevertheless,
fundamental differences between rodents and humans exist.
Conversely, nonhuman primates (NHPs) share many structural
and functional features with humans. NHPs diverged from
humans and formed various lineages: Great Apes (our closest
relatives, Hominidae—e.g., chimpanzees), Old World monkeys
(Cercopithecidae—e.g., baboons, macaques), New World mon-
keys (Parvorder Platyrrhini—e.g., marmosets) and Prosimians
4. (our most distant relatives, the Suborder Strepsirrhini and
Infraorder Tarsiiformes—e.g., lemurs). Therefore, NHPs are
genetically the closest species to humans (Kumar and Hedges,
1998; Finch and Austad, 2012). The purpose of this review is
to explain why the use of NHPs in aging and neurodegener-
ative studies brings additional, sometimes unique information
compared to other animal models.
THE PRIMATE BRAIN ADVANTAGE
In neuroscience, the global understanding of how brain works
in physiological and pathophysiological conditions represents a
major challenge. Brain evolution is characterized by a complex
pattern of species similarities and differences. The neocortex,
also called the “thinking” brain, represents the latest evolu-
tionary stage and brings the capacity, for instance, of planning
complex cognitive behaviors, personality expression, decision-
making and moderating social behavior. These observations
suggest a more complex circuitry that favors local connec-
tivity (Herculano-Houzel et al., 2010) with cognitive conse-
quences (Herculano-Houzel, 2012). Another important point is
the important role played by the primate prefrontal cortex in
“higher” brain functions, such as reasoning, judgment or social
intelligence. Although the total prefrontal cortex volume is
larger
in humans than in other primates, suggesting that humans have
more connections among prefrontal cortex neurons and con-
sequently greater communication (Schoenemann et al., 2005),
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6. Zürcher et al., 2010; Joly et al., 2014). These similarities
between
NHP and human brain in terms of anatomy, gene expression,
neural circuitry, functional and cognitive abilities make of
NHPs
unique, valuable models for neuroscience research. They
provide
a more direct approach that can be translated to human dis-
eases as they allow investigating higher intellectual functions
with
comparative endpoints (Sutcliffe and Hutcheson, 2012).
NONHUMAN PRIMATE MODELS MATTER BECAUSE THEY
FILL THE GAP BETWEEN RODENTS AND HUMANS
Nonanimal experimental approaches play an important role in
the identification/selection of candidate drugs; however,
animal-
based methods are required for toxicity testing. In addition,
the safety of pharmaceuticals must be assessed using nonrodent
models because these tests are carried out with the aim of pro-
tecting human patients in clinical trials. In Europe, all classes
of pharmaceuticals must be tested in NHPs because NHP phar-
macodynamic responses are close to those of humans. We will
illustrate this point with four examples:
(1) Developmental and reproductive toxicology effects are
tested
in NHPs (Chellman et al., 2009), most frequently in
cynomolgus macaque (Macaca fascicularis) (Buse et al., 2003;
Weinbauer et al., 2008) but also in rhesus macaques and mar-
mosets, because of the similar pharmacological responses in
NHPs and humans;
(2) NHP retina has unique features (for instance, both NHPs
and humans have a macula lutea/fovea) not found in other
mammals (Stone and Johnston, 1981);
7. (3) NHP blood coagulation system is more similar to that of
humans than any other species (Abildgaard et al., 1971;
Lewis, 1996);
(4) NHPs are less susceptible to vomiting than other animal
models (Weber, 2005). Therefore, in NHPs, vomiting will not
decrease the exposure to the tested compound and will not
confound the assessment of the early effects of a compound.
Another important phenomenon associated with drug testing in
NHPs, although very difficult to deal with, is the inter-
individual
variability. This variability can be observed for instance in
behav-
ioral studies using the gray mouse lemur (Joly et al., 2006), in
the
response to treatments for Parkinson’s disease in monkeys
(Vezoli
et al., 2011), and also in immune functions (Lebrec, 2013). NHP
inter-individual variability poses real problems in terms of
statis-
tical evaluation of outcomes. However, it mimics what happens
in
humans and therefore helps us to better understand the
variability
within human populations.
NHPs GROW OLD LIKE HUMANS
NHPs have also significantly contributed to understanding aging
and neurodegenerative diseases. Aging NHPs show striking
simi-
larities with elderly humans. Like in humans, age-related
changes
in the glutathione metabolic pathway have been observed in Old
8. World simians (Rathbun and Holleschau, 1992) and in the gray
mouse lemur, in which glutathione-synthase activity decreases
and glutathione-peroxidase activity increases in the lens with
age
(reviewed in Languille et al., 2012). Aging gray mouse lemurs
also
present changes of the sensorial system, especially high suscep-
tibility to cataract (the most frequent ocular lesions observed)
(Beltran et al., 2007), alterations of the biological rhythms and
of the endocrine system (Van Someren and Riemersma-Van Der
Lek, 2007) and a progressive decrease of their motor capacities
(Nemoz-Bertholet and Aujard, 2003). Interestingly, acceleration
of seasonal rhythms (i.e., an annual cycle takes place in 8
months
rather than 1 year by alternating long and short photoperiods)
affects survival and longevity (Perret, 1997). This result
suggests
that longevity could be correlated with the succession of
seasonal
cycles rather than with a fixed biological age. This hypothesis
is
very interesting and it might apply also to human populations.
Indeed, it has been reported that the accumulation of harsh win-
ters may be responsible for a decrease in longevity (Robine et
al.,
2012).
Social interactions are fundamental in primates. For instance,
Picq (1992) suggested that older gray mouse lemur females are
less interested in social contacts than younger females. In rhe-
sus monkeys, a decrease in social interactions with age has been
observed (Heydecke et al., 1986). In chimpanzees, Goodall
(1986)
and Huffman (1990) reported withdrawal from social interac-
tions in older individuals. Sex-based differences in social inter-
actions, social roles and social networks have also been
9. observed
in aging rhesus macaques (Corr, 2003). Altogether, these exam-
ples show that social interactions are of the utmost importance
for aging studies in NHPs and should be used as clear readouts.
THE AGING NHP AND HUMAN BRAIN TRANSCRIPTOMES
ARE SIMILAR
Most of our understanding on the biological changes observed
during aging comes from studies in rodents because they present
clear advantages (short life span, fully characterized genetic
aspects, easy genetic manipulation. . . ). However, rodents and
humans diverged much earlier than humans and NHPs, and this
is likely to have led to fundamental differences in their aging
processes (Messaoudi and Ingram, 2012). In a pioneering work,
Loerch et al. (2008) compared the transcriptome of the cerebral
cortex in aging mice, rhesus macaques and humans, providing
a broad view of the evolution of aging mammalian brain. They
found that only a small subset of age-related gene expression
changes are conserved from mouse to human brain, whereas
such
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Verdier et al. Nonhuman primates in aging and
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changes are highly conserved in rhesus macaques and humans.
Similarly, Marvanová et al. (2003) showed that more than 80%
of genes detected in the human prefrontal cortex have simi-
lar expression profiles also in NHPs. Moreover, the study by
10. Loerch et al. revealed that the major distinguishing feature is
the dramatic, age-related increase in neuronal gene expression
down-regulation, particularly of genes involved in neurotrans-
mission, in humans compared to mice (Loerch et al., 2008).
These major evolutionary changes in the primate cortex are
potentially relevant when studying age-related changes in
cogni-
tion and vulnerability to neurodegeneration. These observations
have been recently corroborated by a transcriptomic analysis,
using human DNA chips (Abdel Rassoul et al., 2010), of the
gene expression profiles in the temporal cortex of young adults,
healthy old animals and “Alzheimer’s disease-like” (“AD-like”)
gray mouse lemurs that naturally present the pathognomonic
lesions of Alzheimer’s disease. The temporal cortex was cho-
sen because this region is connected to the hippocampus and
to the frontal cortex, two structures that are critical for learn-
ing and memory and are altered in Alzheimer’s disease. This
study identified 47 genes that discriminated young from healthy
old and “AD-like” animals. Functional categorization showed
that most of the genes that were up-regulated in healthy old
animals and down-regulated in “AD-like” animals belonged to
metabolic pathways, particularly protein synthesis. These data
suggest the existence of compensatory mechanisms during phys-
iological brain aging that disappear in “AD-like” animals
(Abdel
Rassoul et al., 2010).
NONHUMAN PRIMATES NATURALLY DISPLAY
ALZHEIMER’S
DISEASE LESIONS SUCH AS AMYLOID PLAQUES AND
AGGREGATED HYPERPHOSPHORYLATED TAU PROTEIN
All NHPs naturally display, to various extents depending on
the species, the main pathognomonic lesions of Alzheimer’s dis-
ease (AD): amyloid-beta (Aβ deposits, tau aggregation
(reviewed
in Heuer et al., 2012) and also cortical atrophy. For instance,
11. Aβ plaques and/or tau aggregation have been found in rhe-
sus monkeys (Uno and Walker, 1993; Walker, 1997; Bihaqi and
Zawia, 2013), cynomolgus monkeys (Nakamura et al., 1998),
great apes (Rosen et al., 2008), vervet monkeys (Kalinin et al.,
2013), tamarins (Lemere et al., 2008) and gray mouse lemurs
(Bons et al., 1995; Mestre-Frances et al., 2000). A N-terminal
variant called pyroglutamate-3 Aβ, which is thought to play an
early role in AD pathogenesis, has been detected in the brain of
13–32 year/old Caribbean vervets (Frost et al., 2013). In addi-
tion, based on neuron counting of the subcortical cholinergic
basal forebrain regions (Smith et al., 1999) or imaging studies
(Winkelmann et al., 2012), NHPs show cerebral atrophy and this
feature has been linked to cognitive decline. For instance, in
gray
mouse lemurs, age-related decrease in spatial memory perfor-
mance is related to atrophy of the hippocampus and entorhinal
cortex (Picq et al., 2012), the two regions primarily affected in
AD.
Very recently, Darusman et al. (2014) found in aged
cynomolgus
monkeys a correlation between poor performances in memory
tasks and hippocampus atrophy.
NHPs could also be useful to test new AD therapeutic
approaches, for instance anti-amyloid beta (Aβ) immunotherapy.
The idea is to combat AD by injecting the Aβ peptide, which is
considered to play a central role in AD neuropathology, to trig-
ger an immune response that eventually leads to the production
of antibodies against Aβ. The first attempts in an AD transgenic
mouse model showed that immunization with Aβ42 markedly
reduced the AD-like pathology (Aβ plaque formation, neuritic
dystrophy and astrogliosis) (Schenk et al., 1999). In a follow-up
study in five aged Caribbean vervets, Lemere et al. (2004) val-
idated this paradigm, showing a reduction of cerebral Aβ and
gliosis. This major result generated a great deal of enthusiasm.
12. However, administration of full-length Aβ self-antigen in
humans
(Elan/Wyeth AN-1792 trial) resulted in brain and spinal cord
inflammation and possible micro-hemorrhages (Orgogozo et al.,
2003; Gilman et al., 2005). As a consequence, less toxic Aβ
deriva-
tives have been developed in Tg2576 transgenic mice
(Sigurdsson
et al., 2001). We found that these Aβ derivatives elicit a
substan-
tial antibody response in gray mouse lemurs and, importantly,
that this effect is reversible, thus enhancing the safety profile of
this approach (Trouche et al., 2009). We have also shown iron
accumulation in the choroid plexus with aging by MRI. This
accumulation could be worsened by Aβ-immunization, and this
observation should be a side effect that may be monitored in
therapeutic trials (Joseph-Mathurin et al., 2013).
BREAKTHROUGHS IN PRION RESEARCH THANKS TO THE
USE OF NHPs
Prion diseases are fatal neurodegenerative diseases that affect
humans and animals. Prion diseases are thought to be caused by
transmissible pathogenic agents (“prions”) that can convert a
nor-
mal cellular protein (called PrPc) into the pathogenic,
transmissi-
ble form called PrPSc (reviewed in Fraser, 2014). Among the
dif-
ferent forms of prion diseases, variant Creutzfeldt-Jakob
Disease
(vCJD) received considerable attention in the late 20th cen-
tury because humans can be infected through oral consumption
of animals infected by the bovine spongiform encephalopathy
(BSE) prion strain. NHP-based studies have much contributed to
advancing our knowledge on this disease (reviewed in
Krasemann
13. et al., 2012). For instance, the risk and the mechanisms
associated
with oral transmission have been studied using squirrel monkeys
(Gibbs et al., 1980), cynomolgus macaques (Herzog et al., 2004;
Lasmezas et al., 2005) and gray mouse lemurs (Mestre-Frances
et al., 2012). These studies led to three major conclusions:
(1) The asymptomatic incubation period may be extremely long
(several years), much longer than in the case of intravenous
or intracerebral infection;
(2) The spectrum of tissues harboring BSE infectivity includes
not only brain, but also the lymphoreticular system (spleen,
lymph nodes, appendix, tonsils)
(3) It is possible to estimate the food exposure risk.
These results highlighted the necessity of rapidly introducing
health policy measures to prevent BSE transmission to humans.
Furthermore, the use of NHPs not only improved our knowledge
on the transmissibility of prion strains, but also allowed study-
ing the fine molecular mechanisms involved. For instance,
visual
impairment, associated with retinal damage, is one of the first
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Verdier et al. Nonhuman primates in aging and
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clinical signs of prion disease in Microcebus murinus. We have,
therefore, developed an experimental model system based on the
14. analysis of the retina of gray mouse lemurs to rapidly test
prion-
related neurotoxicity and to develop new therapeutic approaches
(Torrent et al., 2010).
THE MPTP NHP MODELS OF NEURODEGENERATION AND
THE RENAISSANCE OF PARKINSON’S DISEASE
RESEARCH
Based on the observation of early-onset parkinsonism in users
of a
synthetic opioid, 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine
(MPTP), a compound with similar neurotoxic properties, was
further developed. Studies in squirrel monkeys, rhesus
macaques
and marmosets showed that MPTP injections leads to dopamine
depletion in the substantia nigra pars compacta followed by
drastic
cell loss, resting tremor, rigidity and bradykinesia, like in
humans
with Parkinson’s disease (reviewed in Fox and Brotchie, 2010).
Conversely, rodents are not sensitive to MPTP (Capitanio and
Emborg, 2008) and MPTP injections do not lead to the full
spec-
trum of Parkinson’s symptoms in these animals. Importantly,
the MPTP NHP models allowed the identification of the neu-
ral circuits affected in Parkinson’s disease, specifically the role
of
excessive activity in the subthalamic nuclei (Bergman et al.,
1990),
leading to the development of ablative procedures (Baron et al.,
2002) and of deep-brain stimulation of these nuclei (DeLong
and Benabid, 2014). This latter experiments would not have
been
developed without knowing the physiology of the basal ganglia
in nonhuman primates (Baron et al., 2002). The MPTP NHP
models are also used to discover neuroprotective compounds for
15. Parkinson’s and other diseases associated with motor deficits,
such as Huntington disease or Amyotrophic Lateral Sclerosis
(Philippens et al., 2010; Uchida et al., 2012).
CONCLUSION AND PERSPECTIVES
Due to their genetic proximity to humans and their highly
devel-
oped social skills, NHPs are extremely valuable as experimental
animal models. However, as the number of available animals is
restricted for ethical reasons and also because of the high cost
and large space required for breeding colonies, NHPs should
only
be used when no other suitable method is available to fill the
gap of our knowledge. Developing the use of small and
relatively
short-lived NHPs, as proposed by Austad and Fischer (2011),
could lower the costs per animal and facilitate the colony man-
agement and growth. They could be used in preclinical studies
with clear reachable endpoints or in long-term follow-up stud-
ies (equivalent to phase IV in clinical trials) (Lemere et al.,
2004;
Trouche et al., 2009). NHP unique contribution to aging and
neu-
roscience research is well exemplified (Capitanio and Emborg,
2008; Austad and Fischer, 2011; Bihaqi and Zawia, 2013); how-
ever, they are also extremely valuable for studying other
diseases,
such as spinal cord injury (Courtine et al., 2007), infectious
diseases (reviewed in Gardner and Luciw, 2008), respiratory
diseases (Curths et al., 2014), and also for pharmacological
stud-
ies (Nader and Banks, 2014) because their pharmacodynamic
and pharmacokinetic parameters are closely related to those of
humans.
In any case, rodent (or other small animal models) and pri-
16. mate experimental models need to be used in parallel in order to
obtain robust and complementary information. Alongside other
models, nonhuman primates should have a unique place in the
overall aging and neurodegenerative research strategy.
ACKNOWLEDGMENTS
This study is part of a project that has received funding
from the European Community’s 7th Framework Program
(FP7/2007-2013) under grant agreement Nbr 278486 (acronym
“DEVELAGE”), from the Fonds Unique Interministériel and
Région Languedoc-Roussillon under grant agreement Nbr
110284
(acronym “DiaTrAl”), and from the Fondation Plan Alzheimer
(acronym PRADNET). We thank the animal keepers, Sylvie
Rouland, Elisabeth Huetter and Joël Cuoq for animal husbandry.
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Conflict of Interest Statement: The authors declare that the