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Sample records for scaled-up primate brain

  1. The human brain in numbers: a linearly scaled-up primate brain

    Directory of Open Access Journals (Sweden)

    Suzana Herculano-Houzel

    2009-11-01

    Full Text Available The human brain has often been viewed as outstanding among mammalian brains: the most cognitively able, the largest-than-expected from body size, endowed with an overdeveloped cerebral cortex that represents over 80% of brain mass, and purportedly containing 100 billion neurons and 10x more glial cells. Such uniqueness was seemingly necessary to justify the superior cognitive abilities of humans over larger-brained mammals such as elephants and whales. However, our recent studies using a novel method to determine the cellular composition of the brain of humans and other primates as well as of rodents and insectivores show that, since different cellular scaling rules apply to the brains within these orders, brain size can no longer be considered a proxy for the number of neurons in the brain. These studies also showed that the human brain is not exceptional in its cellular composition, as it was found to contain as many neuronal and nonneuronal cells as would be expected of a primate brain of its size. Additionally, the so-called overdeveloped human cerebral cortex holds only 19% of all brain neurons, a fraction that is similar to that found in other mammals. In what regards absolute numbers of neurons, however, the human brain does have two advantages compared to other mammalian brains: compared to rodents, and probably to whales and elephants as well, it is built according to the very economical, space-saving scaling rules that apply to other primates; and, among economically-built primate brains, it is the largest, hence containing the most neurons. These findings argue in favor of a view of cognitive abilities that is centered on absolute numbers of neurons, rather than on body size or encephalization, and call for a re-examination of several concepts related to the exceptionality of the human brain.

  2. The Human Brain in Numbers: A Linearly Scaled-up Primate Brain

    Science.gov (United States)

    Herculano-Houzel, Suzana

    2009-01-01

    The human brain has often been viewed as outstanding among mammalian brains: the most cognitively able, the largest-than-expected from body size, endowed with an overdeveloped cerebral cortex that represents over 80% of brain mass, and purportedly containing 100 billion neurons and 10× more glial cells. Such uniqueness was seemingly necessary to justify the superior cognitive abilities of humans over larger-brained mammals such as elephants and whales. However, our recent studies using a novel method to determine the cellular composition of the brain of humans and other primates as well as of rodents and insectivores show that, since different cellular scaling rules apply to the brains within these orders, brain size can no longer be considered a proxy for the number of neurons in the brain. These studies also showed that the human brain is not exceptional in its cellular composition, as it was found to contain as many neuronal and non-neuronal cells as would be expected of a primate brain of its size. Additionally, the so-called overdeveloped human cerebral cortex holds only 19% of all brain neurons, a fraction that is similar to that found in other mammals. In what regards absolute numbers of neurons, however, the human brain does have two advantages compared to other mammalian brains: compared to rodents, and probably to whales and elephants as well, it is built according to the very economical, space-saving scaling rules that apply to other primates; and, among economically built primate brains, it is the largest, hence containing the most neurons. These findings argue in favor of a view of cognitive abilities that is centered on absolute numbers of neurons, rather than on body size or encephalization, and call for a re-examination of several concepts related to the exceptionality of the human brain. PMID:19915731

  3. Brains, Genes and Primates

    Science.gov (United States)

    Belmonte, Juan Carlos Izpisua; Callaway, Edward M.; Churchland, Patricia; Caddick, Sarah J.; Feng, Guoping; Homanics, Gregg E.; Lee, Kuo-Fen; Leopold, David A.; Miller, Cory T.; Mitchell, Jude F.; Mitalipov, Shoukhrat; Moutri, Alysson R.; Movshon, J. Anthony; Okano, Hideyuki; Reynolds, John H.; Ringach, Dario; Sejnowski, Terrence J.; Silva, Afonso C.; Strick, Peter L.; Wu, Jun; Zhang, Feng

    2015-01-01

    One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward. PMID:25950631

  4. Cellular scaling rules for primate brains

    OpenAIRE

    Herculano-Houzel, Suzana; Collins, Christine E.; Wong, Peiyan; Kaas, Jon H.

    2007-01-01

    Primates are usually found to have richer behavioral repertoires and better cognitive abilities than rodents of similar brain size. This finding raises the possibility that primate brains differ from rodent brains in their cellular composition. Here we examine the cellular scaling rules for primate brains and show that brain size increases approximately isometrically as a function of cell numbers, such that an 11× larger brain is built with 10× more neurons and ≈12× more nonneuronal cells of ...

  5. Binocularity and brain evolution in primates

    OpenAIRE

    Barton, R. A.

    2004-01-01

    Primates are distinguished by frontally directed, highly convergent orbits, which are associated with stereoscopic vision. Although stereoscopic vision requires specialized neural mechanisms, its implications for brain evolution are unknown. Using phylogenetic comparative analysis, I show that evolutionary increases among primate taxa in the degree of orbital convergence correlate with expansion of visual brain structures and, as a consequence, with the overall size of the brain. This pattern...

  6. Gorilla and Orangutan Brains Conform to the Primate Cellular Scaling Rules: Implications for Human Evolution

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    Herculano-Houzel, Suzana; Kaas, Jon H.

    2011-01-01

    Gorillas and orangutans are primates at least as large as humans, but their brains amount to about one third of the size of the human brain. This discrepancy has been used as evidence that the human brain is about 3 times larger than it should be for a primate species of its body size. In contrast to the view that the human brain is special in its size, we have suggested that it is the great apes that might have evolved bodies that are unusually large, on the basis of our recent finding that the cellular composition of the human brain matches that expected for a primate brain of its size, making the human brain a linearly scaled-up primate brain in its number of cells. To investigate whether the brain of great apes also conforms to the primate cellular scaling rules identified previously, we determine the numbers of neuronal and other cells that compose the orangutan and gorilla cerebella, use these numbers to calculate the size of the brain and of the cerebral cortex expected for these species, and show that these match the sizes described in the literature. Our results suggest that the brains of great apes also scale linearly in their numbers of neurons like other primate brains, including humans. The conformity of great apes and humans to the linear cellular scaling rules that apply to other primates that diverged earlier in primate evolution indicates that prehistoric Homo species as well as other hominins must have had brains that conformed to the same scaling rules, irrespective of their body size. We then used those scaling rules and published estimated brain volumes for various hominin species to predict the numbers of neurons that composed their brains. We predict that Homo heidelbergensis and Homo neanderthalensis had brains with approximately 80 billion neurons, within the range of variation found in modern Homo sapiens. We propose that while the cellular scaling rules that apply to the primate brain have remained stable in hominin evolution (since they

  7. Brain size and ecology in small mammals and primates.

    OpenAIRE

    Harvey, P H; Clutton-Brock, T.H; Mace, G. M.

    1980-01-01

    Comparisons of brain-body size relationships within small mammal and primate families reveal intergeneric differences related to diet and foraging strategy. These same associations between relative brain size and ecology are also evident among interfamily comparisons.

  8. Evolution of the brain and intelligence in primates.

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    Roth, Gerhard; Dicke, Ursula

    2012-01-01

    Primates are, on average, more intelligent than other mammals, with great apes and finally humans on top. They generally have larger brains and cortices, and because of higher relative cortex volume and neuron packing density (NPD), they have much more cortical neurons than other mammalian taxa with the same brain size. Likewise, information processing capacity is generally higher in primates due to short interneuronal distance and high axonal conduction velocity. Across primate taxa, differences in intelligence correlate best with differences in number of cortical neurons and synapses plus information processing speed. The human brain stands out by having a large cortical volume with relatively high NPD, high conduction velocity, and high cortical parcellation. All aspects of human intelligence are present at least in rudimentary form in nonhuman primates or some mammals or vertebrates except syntactical language. The latter can be regarded as a very potent "intelligence amplifier." Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Cocaine is pharmacologically active in the nonhuman primate fetal brain

    DEFF Research Database (Denmark)

    Benveniste, Helene; Fowler, Joanna S; Rooney, William D

    2010-01-01

    -trimester pregnant nonhuman primates, cocaine at doses typically used by drug abusers significantly increased brain glucose metabolism to the same extent in the mother as in the fetus (approximately 100%). Inasmuch as brain glucose metabolism is a sensitive marker of brain function, the current findings provide......Cocaine use during pregnancy is deleterious to the newborn child, in part via its disruption of placental blood flow. However, the extent to which cocaine can affect the function of the fetal primate brain is still an unresolved question. Here we used PET and MRI and show that in third...... evidence that cocaine use by a pregnant mother will also affect the function of the fetal brain. We are also unique in showing that cocaine's effects in brain glucose metabolism differed in pregnant (increased) and nonpregnant (decreased) animals, which suggests that the psychoactive effects of cocaine...

  10. Comparative primate neurobiology and the evolution of brain language systems.

    Science.gov (United States)

    Rilling, James K

    2014-10-01

    Human brain specializations supporting language can be identified by comparing human with non-human primate brains. Comparisons with chimpanzees are critical in this endeavor. Human brains are much larger than non-human primate brains, but human language capabilities cannot be entirely explained by brain size. Human brain specializations that potentially support our capacity for language include firstly, wider cortical minicolumns in both Broca's and Wernicke's areas compared with great apes; secondly, leftward asymmetries in Broca's area volume and Wernicke's area minicolumn width that are not found in great apes; and thirdly, arcuate fasciculus projections beyond Wernicke's area to a region of expanded association cortex in the middle and inferior temporal cortex involved in processing word meaning. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Processing Of Visual Information In Primate Brains

    Science.gov (United States)

    Anderson, Charles H.; Van Essen, David C.

    1991-01-01

    Report reviews and analyzes information-processing strategies and pathways in primate retina and visual cortex. Of interest both in biological fields and in such related computational fields as artificial neural networks. Focuses on data from macaque, which has superb visual system similar to that of humans. Authors stress concept of "good engineering" in understanding visual system.

  12. Comparative primate neuroimaging: insights into human brain evolution.

    Science.gov (United States)

    Rilling, James K

    2014-01-01

    Comparative neuroimaging can identify unique features of the human brain and teach us about human brain evolution. Comparisons with chimpanzees, our closest living primate relative, are critical in this endeavor. Structural magnetic resonance imaging (MRI) has been used to compare brain size development, brain structure proportions and brain aging. Positron emission tomography (PET) imaging has been used to compare resting brain glucose metabolism. Functional MRI (fMRI) has been used to compare auditory and visual system pathways, as well as resting-state networks of connectivity. Finally, diffusion-weighted imaging (DWI) has been used to compare structural connectivity. Collectively, these methods have revealed human brain specializations with respect to development, cortical organization, connectivity, and aging. These findings inform our knowledge of the evolutionary changes responsible for the special features of the modern human mind.

  13. Role of brain maturation and reproductive history in the evolution of the primate brain

    Energy Technology Data Exchange (ETDEWEB)

    Sacher, G.A.

    1980-01-01

    All primates conform to a 12% ratio of brain weight to body weight throughout fetal life. This pattern evolved at the beginning of primate evolution, initially as an adaptation to the low energy density of the insect food resource in a strictly arboreal habitat. However, when a wider range of food resources became available, the higher primates retained the 12% trajectory and made it the basis for rapid evolution toward large brain size, which would not have been possible within the restrictions imposed by the 6% brain growth trajectory. The 12% trajectory originally evolved to reduce maternal investment in an energy-poor environment, but became a preadaptation to brain expansion once the energy limitation was overcome by the development of herbivory and frugivory by the higher primates.

  14. Cocaine is pharmacologically active in the nonhuman primate fetal brain

    DEFF Research Database (Denmark)

    Benveniste, Helene; Fowler, Joanna S; Rooney, William D

    2010-01-01

    -trimester pregnant nonhuman primates, cocaine at doses typically used by drug abusers significantly increased brain glucose metabolism to the same extent in the mother as in the fetus (approximately 100%). Inasmuch as brain glucose metabolism is a sensitive marker of brain function, the current findings provide...... evidence that cocaine use by a pregnant mother will also affect the function of the fetal brain. We are also unique in showing that cocaine's effects in brain glucose metabolism differed in pregnant (increased) and nonpregnant (decreased) animals, which suggests that the psychoactive effects of cocaine...... are influenced by the state of pregnancy. Our findings have clinical implications because they imply that the adverse effects of prenatal cocaine exposure to the newborn child include not only cocaine's deleterious effects to the placental circulation, but also cocaine's direct pharmacological effect...

  15. An evolutionarily conserved sexual signature in the primate brain.

    Directory of Open Access Journals (Sweden)

    Björn Reinius

    2008-06-01

    Full Text Available The question of a potential biological sexual signature in the human brain is a heavily disputed subject. In order to provide further insight into this issue, we used an evolutionary approach to identify genes with sex differences in brain expression level among primates. We reasoned that expression patterns important to uphold key male and female characteristics may be conserved during evolution. We selected cortex for our studies because this specific brain region is responsible for many higher behavioral functions. We compared gene expression profiles in the occipital cortex of male and female humans (Homo sapiens, a great ape and cynomolgus macaques (Macaca fascicularis, an old world monkey, two catarrhine species that show abundant morphological sexual dimorphism, as well as in common marmosets (Callithrix Jacchus, a new world monkey which are relatively sexually monomorphic. We identified hundreds of genes with sex-biased expression patterns in humans and macaques, while fewer than ten were differentially expressed between the sexes in marmosets. In primates, a general rule is that many of the morphological and behavioral sexual dimorphisms seen in polygamous species, such as macaques, are typically less pronounced in monogamous species such as the marmosets. Our observations suggest that this correlation may also be reflected in the extent of sex-biased gene expression in the brain. We identified 85 genes with common sex-biased expression, in both human and macaque and 2 genes, X inactivation-specific transcript (XIST and Heat shock factor binding protein 1 (HSBP1, that were consistently sex-biased in the female direction in human, macaque, and marmoset. These observations imply a conserved signature of sexual gene expression dimorphism in cortex of primates. Further, we found that the coding region of female-biased genes is more evolutionarily constrained compared to the coding region of both male-biased and non sex-biased brain

  16. Oral ambroxol increases brain glucocerebrosidase activity in a nonhuman primate

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    Migdalska‐Richards, Anna; Ko, Wai Kin D.; Li, Qin; Bezard, Erwan

    2017-01-01

    Abstract Mutations in the glucocerebrosidase 1 (GBA1) gene are related to both Parkinson disease (PD) and Gaucher disease (GD). In both cases, the condition is associated with deficiency of glucocerebrosidase (GCase), the enzyme encoded by GBA1. Ambroxol is a small molecule chaperone that has been shown in mice to cross the blood‐brain barrier, increase GCase activity and reduce alpha‐synuclein protein levels. In this study, we analyze the effect of ambroxol treatment on GCase activity in healthy nonhuman primates. We show that daily administration of ambroxol results in increased brain GCase activity. Our work further indicates that ambroxol should be investigated as a novel therapy for both PD and neuronopathic GD in humans. PMID:28295625

  17. Coevolution of cultural intelligence, extended life history, sociality, and brain size in primates

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    Street, Sally E.; Navarrete, Ana F.; Laland, Kevin N.

    2017-01-01

    Explanations for primate brain expansion and the evolution of human cognition and culture remain contentious despite extensive research. While multiple comparative analyses have investigated variation in brain size across primate species, very few have addressed why primates vary in how much they use social learning. Here, we evaluate the hypothesis that the enhanced reliance on socially transmitted behavior observed in some primates has coevolved with enlarged brains, complex sociality, and extended lifespans. Using recently developed phylogenetic comparative methods we show that, across primate species, a measure of social learning proclivity increases with absolute and relative brain volume, longevity (specifically reproductive lifespan), and social group size, correcting for research effort. We also confirm relationships of absolute and relative brain volume with longevity (both juvenile period and reproductive lifespan) and social group size, although longevity is generally the stronger predictor. Relationships between social learning, brain volume, and longevity remain when controlling for maternal investment and are therefore not simply explained as a by-product of the generally slower life history expected for larger brained species. Our findings suggest that both brain expansion and high reliance on culturally transmitted behavior coevolved with sociality and extended lifespan in primates. This coevolution is consistent with the hypothesis that the evolution of large brains, sociality, and long lifespans has promoted reliance on culture, with reliance on culture in turn driving further increases in brain volume, cognitive abilities, and lifespans in some primate lineages. PMID:28739950

  18. The Virtual Brain: a simulator of primate brain network dynamics

    Directory of Open Access Journals (Sweden)

    Paula eSanz Leon

    2013-06-01

    Full Text Available We present TheVirtualBrain (TVB, a neuroinformatics platform for full brainnetwork simulations using biologically realistic connectivity. This simulationenvironment enables the model-based inference of neurophysiological mechanismsacross different brain scales that underlie the generation of macroscopicneuroimaging signals including functional MRI (fMRI, EEG and MEG. Researchersfrom different backgrounds can benefit from an integrative software platformincluding a supporting framework for data management (generation,organization, storage, integration and sharing and a simulation core writtenin Python. TVB allows the reproduction and evaluation of personalizedconfigurations of the brain by using individual subject data. Thispersonalization facilitates an exploration of the consequences of pathologicalchanges in the system, permitting to investigate potential ways to counteractsuch unfavorable processes. The architecture of TVB supports interaction withMATLAB packages, for example, the well known Brain Connectivity Toolbox. TVBcan be used in a client-server configuration, such that it can be remotelyaccessed through the Internet thanks to its web-basedHTML5, JS and WebGL graphical user interface. TVB is alsoaccessible as a standalone cross-platform Python library and application, andusers can interact with the scientific core through the scripting interfaceIDLE, enabling easy modeling, development and debugging of the scientifickernel. This second interface makes TVB extensible by combining it with otherlibraries and modules developed by the Python scientific community. In this article, we describe the theoretical background and foundations that led to thedevelopment of TVB, the architecture and features of its major softwarecomponents as well as potential neuroscience applications.

  19. The Virtual Brain: a simulator of primate brain network dynamics.

    Science.gov (United States)

    Sanz Leon, Paula; Knock, Stuart A; Woodman, M Marmaduke; Domide, Lia; Mersmann, Jochen; McIntosh, Anthony R; Jirsa, Viktor

    2013-01-01

    We present The Virtual Brain (TVB), a neuroinformatics platform for full brain network simulations using biologically realistic connectivity. This simulation environment enables the model-based inference of neurophysiological mechanisms across different brain scales that underlie the generation of macroscopic neuroimaging signals including functional MRI (fMRI), EEG and MEG. Researchers from different backgrounds can benefit from an integrative software platform including a supporting framework for data management (generation, organization, storage, integration and sharing) and a simulation core written in Python. TVB allows the reproduction and evaluation of personalized configurations of the brain by using individual subject data. This personalization facilitates an exploration of the consequences of pathological changes in the system, permitting to investigate potential ways to counteract such unfavorable processes. The architecture of TVB supports interaction with MATLAB packages, for example, the well known Brain Connectivity Toolbox. TVB can be used in a client-server configuration, such that it can be remotely accessed through the Internet thanks to its web-based HTML5, JS, and WebGL graphical user interface. TVB is also accessible as a standalone cross-platform Python library and application, and users can interact with the scientific core through the scripting interface IDLE, enabling easy modeling, development and debugging of the scientific kernel. This second interface makes TVB extensible by combining it with other libraries and modules developed by the Python scientific community. In this article, we describe the theoretical background and foundations that led to the development of TVB, the architecture and features of its major software components as well as potential neuroscience applications.

  20. Oxytocin and Serotonin Brain Mechanisms in the Nonhuman Primate.

    Science.gov (United States)

    Lefevre, Arthur; Richard, Nathalie; Jazayeri, Mina; Beuriat, Pierre-Aurélien; Fieux, Sylvain; Zimmer, Luc; Duhamel, Jean-René; Sirigu, Angela

    2017-07-12

    Oxytocin (OT) is increasingly studied for its therapeutic potential in psychiatric disorders, which are associated with the deregulation of several neurotransmission systems. Studies in rodents demonstrated that the interaction between OT and serotonin (5-HT) is critical for several aspects of social behavior. Using PET scan in humans, we have recently found that 5-HT 1A receptor (5-HT 1A R) function is modified after intranasal oxytocin intake. However, the underlying mechanism between OT and 5-HT remains unclear. To understand this interaction, we tested 3 male macaque monkeys using both [ 11 C]DASB and [ 18 F]MPPF, two PET radiotracers, marking the serotonin transporter and the 5-HT 1A R, respectively. Oxytocin (1 IU in 20 μl of ACSF) or placebo was injected into the brain lateral ventricle 45 min before scans. Additionally, we performed postmortem autoradiography. Compared with placebo, OT significantly reduced [ 11 C]DASB binding potential in right amygdala, insula, and hippocampus, whereas [ 18 F]MPPF binding potential increased in right amygdala and insula. Autoradiography revealed that [ 11 C]DASB was sensitive to physiological levels of 5-HT modification, and that OT does not act directly on the 5-HT 1A R. Our results show that oxytocin administration in nonhuman primates influences serotoninergic neurotransmission via at least two ways: (1) by provoking a release of serotonin in key limbic regions; and (2) by increasing the availability of 5-HT 1A R receptors in the same limbic areas. Because these two molecules are important for social behavior, our study sheds light on the specific nature of their interaction, therefore helping to develop new mechanisms-based therapies for psychiatric disorders. SIGNIFICANCE STATEMENT Social behavior is largely controlled by brain neuromodulators, such as oxytocin and serotonin. While these are currently targeted in the context of psychiatric disorders such as autism and schizophrenia, a new promising pharmaceutical

  1. Behavioral and brain asymmetries in primates: a preliminary evaluation of two evolutionary hypotheses.

    Science.gov (United States)

    Hopkins, William D; Misiura, Maria; Pope, Sarah M; Latash, Elitaveta M

    2015-11-01

    Contrary to many historical views, recent evidence suggests that species-level behavioral and brain asymmetries are evident in nonhuman species. Here, we briefly present evidence of behavioral, perceptual, cognitive, functional, and neuroanatomical asymmetries in nonhuman primates. In addition, we describe two historical accounts of the evolutionary origins of hemispheric specialization and present data from nonhuman primates that address these specific theories. Specifically, we first discuss the evidence that genes play specific roles in determining left-right differences in anatomical and functional asymmetries in primates. We next consider and present data on the hypothesis that hemispheric specialization evolved as a by-product of increasing brain size relative to the surface area of the corpus callosum in different primate species. Last, we discuss some of the challenges in the study of hemispheric specialization in primates and offer some suggestions on how to advance the field. © 2015 New York Academy of Sciences.

  2. Cellular Scaling Rules for the Brains of an Extended Number of Primate Species

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    Gabi, Mariana; Collins, Christine E.; Wong, Peiyan; Torres, Laila B.; Kaas, Jon H.; Herculano-Houzel, Suzana

    2010-01-01

    What are the rules relating the size of the brain and its structures to the number of cells that compose them and their average sizes? We have shown previously that the cerebral cortex, cerebellum and the remaining brain structures increase in size as a linear function of their numbers of neurons and non-neuronal cells across 6 species of primates. Here we describe that the cellular composition of the same brain structures of 5 other primate species, as well as humans, conform to the scaling rules identified previously, and that the updated power functions for the extended sample are similar to those determined earlier. Accounting for phylogenetic relatedness in the combined dataset does not affect the scaling slopes that apply to the cerebral cortex and cerebellum, but alters the slope for the remaining brain structures to a value that is similar to that observed in rodents, which raises the possibility that the neuronal scaling rules for these structures are shared among rodents and primates. The conformity of the new set of primate species to the previous rules strongly suggests that the cellular scaling rules we have identified apply to primates in general, including humans, and not only to particular subgroups of primate species. In contrast, the allometric rules relating body and brain size are highly sensitive to the particular species sampled, suggesting that brain size is neither determined by body size nor together with it, but is rather only loosely correlated with body size. PMID:20926854

  3. Primate aging in the mammalian scheme: the puzzle of extreme variation in brain aging.

    Science.gov (United States)

    Finch, Caleb E; Austad, Steven N

    2012-10-01

    At later ages, humans have high risk of developing Alzheimer disease (AD) which may afflict up to 50% by 90 years. While prosimians and monkeys show more substantial changes, the great apes brains examined show mild neurodegenerative changes. Compared with rodents, primates develop and reproduce slowly and are long lived. The New World primates contain some of the shortest as well as some of the longest-lived monkey species, while the prosimians develop the most rapidly and are the shortest lived. Great apes have the largest brains, slowest development, and longest lives among the primates. All primates share some level of slowly progressive, age-related neurodegenerative changes. However, no species besides humans has yet shown regular drastic neuron loss or cognitive decline approaching clinical grade AD. Several primates accumulate extensive deposits of diffuse amyloid-beta protein (Aβ) but only a prosimian-the gray mouse lemur-regularly develops a tauopathy approaching the neurofibrillary tangles of AD. Compared with monkeys, nonhuman great apes display even milder brain-aging changes, a deeply puzzling observation. The genetic basis for these major species differences in brain aging remains obscure but does not involve the Aβ coding sequence which is identical in nonhuman primates and humans. While chimpanzees merit more study, we note the value of smaller, shorter-lived species such as marmosets and small lemurs for aging studies. A continuing concern for all aging studies employing primates is that relative to laboratory rodents, primate husbandry is in a relatively primitive state, and better husbandry to control infections and obesity is needed for brain aging research.

  4. Evidence for Conversion of Methanol to Formaldehyde in Nonhuman Primate Brain.

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    Zhai, Rongwei; Zheng, Na; Rizak, Joshua; Hu, Xintian

    2016-01-01

    Many studies have reported that methanol toxicity to primates is mainly associated with its metabolites, formaldehyde (FA) and formic acid. While methanol metabolism and toxicology have been best studied in peripheral organs, little study has focused on the brain and no study has reported experimental evidence that demonstrates transformation of methanol into FA in the primate brain. In this study, three rhesus macaques were given a single intracerebroventricular injection of methanol to investigate whether a metabolic process of methanol to FA occurs in nonhuman primate brain. Levels of FA in cerebrospinal fluid (CSF) were then assessed at different time points. A significant increase of FA levels was found at the 18th hour following a methanol injection. Moreover, the FA level returned to a normal physiological level at the 30th hour after the injection. These findings provide direct evidence that methanol is oxidized to FA in nonhuman primate brain and that a portion of the FA generated is released out of the brain cells. This study suggests that FA is produced from methanol metabolic processes in the nonhuman primate brain and that FA may play a significant role in methanol neurotoxicology.

  5. Estrogen regulation of microcephaly genes and evolution of brain sexual dimorphism in primates.

    Science.gov (United States)

    Shi, Lei; Lin, Qiang; Su, Bing

    2015-06-30

    Sexual dimorphism in brain size is common among primates, including humans, apes and some Old World monkeys. In these species, the brain size of males is generally larger than that of females. Curiously, this dimorphism has persisted over the course of primate evolution and human origin, but there is no explanation for the underlying genetic controls that have maintained this disparity in brain size. In the present study, we tested the effect of the female hormone (estradiol) on seven genes known to be related to brain size in both humans and nonhuman primates, and we identified half estrogen responsive elements (half EREs) in the promoter regions of four genes (MCPH1, ASPM, CDK5RAP2 and WDR62). Likewise, at sequence level, it appears that these half EREs are generally conserved across primates. Later testing via a reporter gene assay and cell-based endogenous expression measurement revealed that estradiol could significantly suppress the expression of the four affected genes involved in brain size. More intriguingly, when the half EREs were deleted from the promoters, the suppression effect disappeared, suggesting that the half EREs mediate the regulation of estradiol on the brain size genes. We next replicated these experiments using promoter sequences from chimpanzees and rhesus macaques, and observed a similar suppressive effect of estradiol on gene expression, suggesting that this mechanism is conserved among primate species that exhibit brain size dimorphism. Brain size dimorphism among certain primates, including humans, is likely regulated by estrogen through its sex-dependent suppression of brain size genes during development.

  6. Evolution of ASPM is associated with both increases and decreases in brain size in primates.

    Science.gov (United States)

    Montgomery, Stephen H; Mundy, Nicholas I

    2012-03-01

    A fundamental trend during primate evolution has been the expansion of brain size. However, this trend was reversed in the Callitrichidae (marmosets and tamarins), which have secondarily evolved smaller brains associated with a reduction in body size. The recent pursuit of the genetic basis of brain size evolution has largely focused on episodes of brain expansion, but new insights may be gained by investigating episodes of brain size reduction. Previous results suggest two genes (ASPM and CDK5RAP2) associated with microcephaly, a human neurodevelopmental disorder, may have an evolutionary function in primate brain expansion. Here we use new sequences encoding key functional domains from 12 species of callitrichids to show that positive selection has acted on ASPM across callitrichid evolution and the rate of ASPM evolution is significantly negatively correlated with callitrichid brain size, whereas the evolution of CDK5RAP2 shows no correlation with brain size. Our findings strongly suggest that ASPM has a previously unsuspected role in the evolution of small brains in primates. ASPM is therefore intimately linked to both evolutionary increases and decreases in brain size in anthropoids and is a key target for natural selection acting on brain size. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

  7. Reconstructing the ups and downs of primate brain evolution: implications for adaptive hypotheses and Homo floresiensis

    Directory of Open Access Journals (Sweden)

    Barton Robert A

    2010-01-01

    Full Text Available Abstract Background Brain size is a key adaptive trait. It is often assumed that increasing brain size was a general evolutionary trend in primates, yet recent fossil discoveries have documented brain size decreases in some lineages, raising the question of how general a trend there was for brains to increase in mass over evolutionary time. We present the first systematic phylogenetic analysis designed to answer this question. Results We performed ancestral state reconstructions of three traits (absolute brain mass, absolute body mass, relative brain mass using 37 extant and 23 extinct primate species and three approaches to ancestral state reconstruction: parsimony, maximum likelihood and Bayesian Markov-chain Monte Carlo. Both absolute and relative brain mass generally increased over evolutionary time, but body mass did not. Nevertheless both absolute and relative brain mass decreased along several branches. Applying these results to the contentious case of Homo floresiensis, we find a number of scenarios under which the proposed evolution of Homo floresiensis' small brain appears to be consistent with patterns observed along other lineages, dependent on body mass and phylogenetic position. Conclusions Our results confirm that brain expansion began early in primate evolution and show that increases occurred in all major clades. Only in terms of an increase in absolute mass does the human lineage appear particularly striking, with both the rate of proportional change in mass and relative brain size having episodes of greater expansion elsewhere on the primate phylogeny. However, decreases in brain mass also occurred along branches in all major clades, and we conclude that, while selection has acted to enlarge primate brains, in some lineages this trend has been reversed. Further analyses of the phylogenetic position of Homo floresiensis and better body mass estimates are required to confirm the plausibility of the evolution of its small brain

  8. Epigenomic annotation of gene regulatory alterations during evolution of the primate brain

    NARCIS (Netherlands)

    Vermunt, Marit W; Tan, Sander C; Castelijns, Bas; Geeven, Geert; Reinink, Peter; de Bruijn, Ewart; Kondova, Ivanela; Persengiev, Stephan; Bontrop, Ronald; Cuppen, Edwin; de Laat, Wouter; Creyghton, Menno P

    Although genome sequencing has identified numerous noncoding alterations between primate species, which of those are regulatory and potentially relevant to the evolution of the human brain is unclear. Here we annotated cis-regulatory elements (CREs) in the human, rhesus macaque and chimpanzee

  9. Social learning, culture and the 'socio-cultural brain' of human and non-human primates.

    Science.gov (United States)

    Whiten, Andrew; van de Waal, Erica

    2017-11-01

    Noting important recent discoveries, we review primate social learning, traditions and culture, together with associated findings about primate brains. We survey our current knowledge of primate cultures in the wild, and complementary experimental diffusion studies testing species' capacity to sustain traditions. We relate this work to theories that seek to explain the enlarged brain size of primates as specializations for social intelligence, that have most recently extended to learning from others and the cultural transmission this permits. We discuss alternative theories and review a variety of recent findings that support cultural intelligence hypotheses for primate encephalization. At a more fine-grained neuroscientific level we focus on the underlying processes of social learning, especially emulation and imitation. Here, our own and others' recent research has established capacities for bodily imitation in both monkeys and apes, results that are consistent with a role for the mirror neuron system in social learning. We review important convergences between behavioural findings and recent non-invasive neuroscientific studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. ScaleUp America Communities

    Data.gov (United States)

    Small Business Administration — SBA’s new ScaleUp America Initiative is designed to help small firms with high potential “scale up” and grow their businesses so that they will provide more jobs and...

  11. Evidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primates

    Science.gov (United States)

    Harrison, Peter W.; Caravas, Jason A.; Raghanti, Mary Ann; Phillips, Kimberley A.; Mundy, Nicholas I.

    2017-01-01

    The adaptive significance of human brain evolution has been frequently studied through comparisons with other primates. However, the evolution of increased brain size is not restricted to the human lineage but is a general characteristic of primate evolution. Whether or not these independent episodes of increased brain size share a common genetic basis is unclear. We sequenced and de novo assembled the transcriptome from the neocortical tissue of the most highly encephalized nonhuman primate, the tufted capuchin monkey (Cebus apella). Using this novel data set, we conducted a genome-wide analysis of orthologous brain-expressed protein coding genes to identify evidence of conserved gene–phenotype associations and species-specific adaptations during three independent episodes of brain size increase. We identify a greater number of genes associated with either total brain mass or relative brain size across these six species than show species-specific accelerated rates of evolution in individual large-brained lineages. We test the robustness of these associations in an expanded data set of 13 species, through permutation tests and by analyzing how genome-wide patterns of substitution co-vary with brain size. Many of the genes targeted by selection during brain expansion have glutamatergic functions or roles in cell cycle dynamics. We also identify accelerated evolution in a number of individual capuchin genes whose human orthologs are associated with human neuropsychiatric disorders. These findings demonstrate the value of phenotypically informed genome analyses, and suggest at least some aspects of human brain evolution have occurred through conserved gene–phenotype associations. Understanding these commonalities is essential for distinguishing human-specific selection events from general trends in brain evolution. PMID:28391320

  12. Evidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primates.

    Science.gov (United States)

    Boddy, Amy M; Harrison, Peter W; Montgomery, Stephen H; Caravas, Jason A; Raghanti, Mary Ann; Phillips, Kimberley A; Mundy, Nicholas I; Wildman, Derek E

    2017-03-01

    The adaptive significance of human brain evolution has been frequently studied through comparisons with other primates. However, the evolution of increased brain size is not restricted to the human lineage but is a general characteristic of primate evolution. Whether or not these independent episodes of increased brain size share a common genetic basis is unclear. We sequenced and de novo assembled the transcriptome from the neocortical tissue of the most highly encephalized nonhuman primate, the tufted capuchin monkey (Cebus apella). Using this novel data set, we conducted a genome-wide analysis of orthologous brain-expressed protein coding genes to identify evidence of conserved gene-phenotype associations and species-specific adaptations during three independent episodes of brain size increase. We identify a greater number of genes associated with either total brain mass or relative brain size across these six species than show species-specific accelerated rates of evolution in individual large-brained lineages. We test the robustness of these associations in an expanded data set of 13 species, through permutation tests and by analyzing how genome-wide patterns of substitution co-vary with brain size. Many of the genes targeted by selection during brain expansion have glutamatergic functions or roles in cell cycle dynamics. We also identify accelerated evolution in a number of individual capuchin genes whose human orthologs are associated with human neuropsychiatric disorders. These findings demonstrate the value of phenotypically informed genome analyses, and suggest at least some aspects of human brain evolution have occurred through conserved gene-phenotype associations. Understanding these commonalities is essential for distinguishing human-specific selection events from general trends in brain evolution. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  13. A simpler primate brain: the visual system of the marmoset monkey

    Directory of Open Access Journals (Sweden)

    Samuel Gavan Solomon

    2014-08-01

    Full Text Available Humans are diurnal primates with high visual acuity at the centre of gaze. Although primates share many similarities in the organisation of their visual centres with other mammals, and even other species of vertebrates, their visual pathways also show unique features, particularly with respect to the organization of the cerebral cortex. Therefore, in order to understand some aspects of human visual function, we need to study non-human primate brains. Which species is the most appropriate model? Macaque monkeys, the most widely used non-human primates, are not an optimal choice in many practical respects. For example, much of the macaque cerebral cortex is buried within sulci, and is therefore inaccessible to many imaging techniques, and the postnatal development and lifespan of macaques are prohibitively long for many studies of brain maturation, plasticity and ageing. In these and several other respects the marmoset, a small New World monkey, represents a more appropriate choice. Here we review the visual pathways of the marmoset, highlighting recent work that brings these advantages into focus, and identify where additional work needs to be done to link marmoset brain organisation to that of macaques and humans. We will argue that the marmoset monkey provides a good subject for studies of a complex visual system, which will likely allow an important bridge linking experiments in animal models to humans.

  14. SYNAPTOSOMAL LACTATE DEHYDROGENASE ISOENZYME COMPOSITION IS SHIFTED TOWARD AEROBIC FORMS IN PRIMATE BRAIN EVOLUTION

    Science.gov (United States)

    Duka, Tetyana; Anderson, Sarah M.; Collins, Zachary; Raghanti, Mary Ann; Ely, John J.; Hof, Patrick R.; Wildman, Derek E.; Goodman, Morris; Grossman, Lawrence I.; Sherwood, Chet C.

    2014-01-01

    With the evolution of a relatively large brain size in haplorhine primates (i.e., tarsiers, monkeys, apes and humans), there have been associated changes in the molecular machinery that delivers energy to the neocortex. Here we investigated variation in lactate dehydrogenase (LDH) expression and isoenzyme composition of the neocortex and striatum in primates using quantitative Western blotting and isoenzyme analysis of total homogenates and synaptosomal fractions. Analysis of isoform expression revealed that LDH in the synaptosomal fraction from both forebrain regions shifted towards a predominance of the heart-type, aerobic isoforms, LDHB, among haplorhines as compared to strepsirrhines (i.e., lorises and lemurs), while in total homogenate of neocortex and striatum there was no significant difference in the LDH isoenzyme composition between the primate suborders. The largest increase occurred in synapse-associated LDH-B expression in the neocortex, displaying an especially remarkable elevation in the ratio of LDH-B to LDH-A in humans. The phylogenetic variation in LDH-B to LDH-A ratio was correlated with species typical brain mass, but not encephalization quotient. A significant LDHB increase in the sub-neuronal fraction from haplorhine neocortex and striatum suggests a relatively higher rate of aerobic glycolysis that is linked to synaptosomal mitochondrial metabolism. Our results indicate that there is differential composition of LDH isoenzymes and metabolism in synaptic terminals that evolved in primates to meet increased energy requirements in association with brain enlargement. PMID:24686273

  15. Spectrum of Infantile Esotropia in Primates: Behavior, Brains and Orbits

    Science.gov (United States)

    Tychsen, Lawrence; Richards, Michael; Wong, Agnes; Foeller, Paul; Burhkalter, Andreas; Narasimhan, Anita; Demer, Joseph

    2009-01-01

    Introduction Recent studies of human infants have described a spectrum of early-onset esotropia, from small-variable-angle to large heterotropias.1 We report here a similar spectrum of early-onset esotropia in infant monkeys, with emphasis on the relationship between visuomotor deficits, central nervous system (CNS) circuitry and orbital anatomy. Methods Eye movements were recorded in macaque monkeys with natural, infantile-onset esotropia (n=7) and in control monkeys (n=2) to assess alignment, latent nystagmus, dissociated vertical deviation (DVD), and pursuit/optokinetic nystagmus (OKN) asymmetries. Acuity was measured by preferential-looking technique or spatial sweep VEP (SSVEP). Geniculo-striate pathways were then analyzed with neuroanatomic tracers and metabolic labels. Extraocular muscles were examined by high-resolution magnetic resonance imaging (MRI) and anatomic sectioning of whole orbits. Results Esotropia ranged from 4-13.5° (7-24 prism diopters [PD]) with fixation preference (if any) varying idiosyncratically (as in human). Severity of ocular motor dysfunction (i.e. nystagmus velocity, DVD amplitude, pursuit-OKN nasal bias index), increased as the magnitude of esotropia angle. Animals with greater ocular motor deficits tended to have greater visual area V1 (striate cortex) neuroanatomic deficits, evident as fewer binocular horizontal connections in V1. Orbital MRI/anatomic analysis showed no difference in horizontal rectus cross sectional areas, muscle paths, innervation densities or cytoarchitecture compared to normal animals. Conclusion The infantile esotropia spectrum in non-human primates is remarkably similar to that reported in human infants. Concomitant esotropia in these primates cannot be ascribed to abnormalities of the extraocular muscles or orbit. These findings, combined with epidemiologic studies of human, suggest that perturbations of CNS binocular pathways in early development are the primary cause of the infantile esotropia syndrome

  16. Enhanced brain distribution of carboplatin in a primate model after blood-brain barrier disruption using an implantable ultrasound device.

    Science.gov (United States)

    Goldwirt, Lauriane; Canney, Michael; Horodyckid, Catherine; Poupon, Joel; Mourah, Samia; Vignot, Alexandre; Chapelon, Jean-Yves; Carpentier, Alexandre

    2016-01-01

    Glioblastoma is both the most common and aggressive primary brain tumor in adults. Carboplatin chemotherapy has shown only modest efficacy in progressive high-grade gliomas. The limited clinical efficacy of carboplatin may be due to its low concentration in tissue when the drug is delivered intravenously. The aim of this study was to assess whether the tissue concentration of intravenously administered carboplatin could be enhanced by ultrasound-induced blood-brain disruption in a primate model. Carboplatin was administered intravenously for 60 min to a single primate following blood-brain barrier opening induced by an implantable ultrasound device. Blood and brain samples were collected after animal killing, which occurred 60 min after the end of carboplatin administration. Platinum quantification in ultrafiltrate plasma and brain samples was performed using inductively coupled plasma mass spectrometry. The brain concentration of platinum was highly enhanced (5.2×) in the 3.9 cm(3) region sonicated by the US beam, with a higher concentration in more vascularized anatomical structures. At 5 and 10 mm from the US beam axis, platinum concentrations were slightly enhanced (2.2× and 1.3× respectively). This study demonstrates that BBB opening using an implantable ultrasound transducer enhances the brain distribution of carboplatin in a loco-regional manner. Such a treatment approach is of significant interest for the treatment of primary brain tumors and is under current evaluation in a phase 1 clinical trial (NCT02253212).

  17. Male and female brain evolution is subject to contrasting selection pressures in primates

    Science.gov (United States)

    Dunbar, Robin IM

    2007-01-01

    The claim that differences in brain size across primate species has mainly been driven by the demands of sociality (the "social brain" hypothesis) is now widely accepted. Some of the evidence to support this comes from the fact that species that live in large social groups have larger brains, and in particular larger neocortices. Lindenfors and colleagues (BMC Biology 5:20) add significantly to our appreciation of this process by showing that there are striking differences between the two sexes in the social mechanisms and brain units involved. Female sociality (which is more affiliative) is related most closely to neocortex volume, but male sociality (which is more competitive and combative) is more closely related to subcortical units (notably those associated with emotional responses). Thus different brain units have responded to different selection pressures. PMID:17493267

  18. Male and female brain evolution is subject to contrasting selection pressures in primates

    Directory of Open Access Journals (Sweden)

    Dunbar Robin IM

    2007-05-01

    Full Text Available Abstract The claim that differences in brain size across primate species has mainly been driven by the demands of sociality (the "social brain" hypothesis is now widely accepted. Some of the evidence to support this comes from the fact that species that live in large social groups have larger brains, and in particular larger neocortices. Lindenfors and colleagues (BMC Biology 5:20 add significantly to our appreciation of this process by showing that there are striking differences between the two sexes in the social mechanisms and brain units involved. Female sociality (which is more affiliative is related most closely to neocortex volume, but male sociality (which is more competitive and combative is more closely related to subcortical units (notably those associated with emotional responses. Thus different brain units have responded to different selection pressures.

  19. Social intelligence, innovation, and enhanced brain size in primates

    NARCIS (Netherlands)

    Reader, S.M.; Laland, K.N.

    2002-01-01

    Despite considerable current interest in the evolution of intelligence, the intuitively appealing notion that brain volume and ‘‘intelligence’’ are linked remains untested. Here, we use ecologically relevant measures of cognitive ability, the reported incidence of behavioral innovation, social

  20. Oral ambroxol increases brain glucocerebrosidase activity in a nonhuman primate

    OpenAIRE

    Migdalska-Richards, A.; Ko, W. K. D.; Li, Q.; Bezard, E.; Schapira, A H V

    2017-01-01

    Abstract Mutations in the glucocerebrosidase 1 (GBA1) gene are related to both Parkinson disease (PD) and Gaucher disease (GD). In both cases, the condition is associated with deficiency of glucocerebrosidase (GCase), the enzyme encoded by GBA1. Ambroxol is a small molecule chaperone that has been shown in mice to cross the blood?brain barrier, increase GCase activity and reduce alpha?synuclein protein levels. In this study, we analyze the effect of ambroxol treatment on GCase activity in hea...

  1. Rate of evolution in brain-expressed genes in humans and other primates.

    Directory of Open Access Journals (Sweden)

    Hurng-Yi Wang

    2007-02-01

    Full Text Available Brain-expressed genes are known to evolve slowly in mammals. Nevertheless, since brains of higher primates have evolved rapidly, one might expect acceleration in DNA sequence evolution in their brain-expressed genes. In this study, we carried out full-length cDNA sequencing on the brain transcriptome of an Old World monkey (OWM and then conducted three-way comparisons among (i mouse, OWM, and human, and (ii OWM, chimpanzee, and human. Although brain-expressed genes indeed appear to evolve more rapidly in species with more advanced brains (apes > OWM > mouse, a similar lineage effect is observable for most other genes. The broad inclusion of genes in the reference set to represent the genomic average is therefore critical to this type of analysis. Calibrated against the genomic average, the rate of evolution among brain-expressed genes is probably lower (or at most equal in humans than in chimpanzee and OWM. Interestingly, the trend of slow evolution in coding sequence is no less pronounced among brain-specific genes, vis-à-vis brain-expressed genes in general. The human brain may thus differ from those of our close relatives in two opposite directions: (i faster evolution in gene expression, and (ii a likely slowdown in the evolution of protein sequences. Possible explanations and hypotheses are discussed.

  2. Aging and Gene Expression in the Primate Brain

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.; Paabo, Svante; Eisen, Michael B.

    2005-02-18

    It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

  3. Aging and gene expression in the primate brain.

    Directory of Open Access Journals (Sweden)

    Hunter B Fraser

    2005-09-01

    Full Text Available It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

  4. Cortical network architecture for context processing in primate brain.

    Science.gov (United States)

    Chao, Zenas C; Nagasaka, Yasuo; Fujii, Naotaka

    2015-09-29

    Context is information linked to a situation that can guide behavior. In the brain, context is encoded by sensory processing and can later be retrieved from memory. How context is communicated within the cortical network in sensory and mnemonic forms is unknown due to the lack of methods for high-resolution, brain-wide neuronal recording and analysis. Here, we report the comprehensive architecture of a cortical network for context processing. Using hemisphere-wide, high-density electrocorticography, we measured large-scale neuronal activity from monkeys observing videos of agents interacting in situations with different contexts. We extracted five context-related network structures including a bottom-up network during encoding and, seconds later, cue-dependent retrieval of the same network with the opposite top-down connectivity. These findings show that context is represented in the cortical network as distributed communication structures with dynamic information flows. This study provides a general methodology for recording and analyzing cortical network neuronal communication during cognition.

  5. Characterizing Focused-Ultrasound Mediated Drug Delivery to the Heterogeneous Primate Brain In Vivo with Acoustic Monitoring

    Science.gov (United States)

    Wu, Shih-Ying; Sanchez, Carlos Sierra; Samiotaki, Gesthimani; Buch, Amanda; Ferrera, Vincent P.; Konofagou, Elisa E.

    2016-11-01

    Focused ultrasound with microbubbles has been used to noninvasively and selectively deliver pharmacological agents across the blood-brain barrier (BBB) for treating brain diseases. Acoustic cavitation monitoring could serve as an on-line tool to assess and control the treatment. While it demonstrated a strong correlation in small animals, its translation to primates remains in question due to the anatomically different and highly heterogeneous brain structures with gray and white matteras well as dense vasculature. In addition, the drug delivery efficiency and the BBB opening volume have never been shown to be predictable through cavitation monitoring in primates. This study aimed at determining how cavitation activity is correlated with the amount and concentration of gadolinium delivered through the BBB and its associated delivery efficiency as well as the BBB opening volume in non-human primates. Another important finding entails the effect of heterogeneous brain anatomy and vasculature of a primate brain, i.e., presence of large cerebral vessels, gray and white matter that will also affect the cavitation activity associated with variation of BBB opening in different tissue types, which is not typically observed in small animals. Both these new findings are critical in the primate brain and provide essential information for clinical applications.

  6. Scaling up of renewable chemicals.

    Science.gov (United States)

    Sanford, Karl; Chotani, Gopal; Danielson, Nathan; Zahn, James A

    2016-04-01

    The transition of promising technologies for production of renewable chemicals from a laboratory scale to commercial scale is often difficult and expensive. As a result the timeframe estimated for commercialization is typically underestimated resulting in much slower penetration of these promising new methods and products into the chemical industries. The theme of 'sugar is the next oil' connects biological, chemical, and thermochemical conversions of renewable feedstocks to products that are drop-in replacements for petroleum derived chemicals or are new to market chemicals/materials. The latter typically offer a functionality advantage and can command higher prices that result in less severe scale-up challenges. However, for drop-in replacements, price is of paramount importance and competitive capital and operating expenditures are a prerequisite for success. Hence, scale-up of relevant technologies must be interfaced with effective and efficient management of both cell and steel factories. Details involved in all aspects of manufacturing, such as utilities, sterility, product recovery and purification, regulatory requirements, and emissions must be managed successfully. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. The SCALE-UP Project

    Science.gov (United States)

    Beichner, Robert

    2015-03-01

    The Student Centered Active Learning Environment with Upside-down Pedagogies (SCALE-UP) project was developed nearly 20 years ago as an economical way to provide collaborative, interactive instruction even for large enrollment classes. Nearly all research-based pedagogies have been designed with fairly high faculty-student ratios. The economics of introductory courses at large universities often precludes that situation, so SCALE-UP was created as a way to facilitate highly collaborative active learning with large numbers of students served by only a few faculty and assistants. It enables those students to learn and succeed not only in acquiring content, but also to practice important 21st century skills like problem solving, communication, and teamsmanship. The approach was initially targeted at undergraduate science and engineering students taking introductory physics courses in large enrollment sections. It has since expanded to multiple content areas, including chemistry, math, engineering, biology, business, nursing, and even the humanities. Class sizes range from 24 to over 600. Data collected from multiple sites around the world indicates highly successful implementation at more than 250 institutions. NSF support was critical for initial development and dissemination efforts. Generously supported by NSF (9752313, 9981107) and FIPSE (P116B971905, P116B000659).

  8. Two areas for familiar face recognition in the primate brain.

    Science.gov (United States)

    Landi, Sofia M; Freiwald, Winrich A

    2017-08-11

    Familiarity alters face recognition: Familiar faces are recognized more accurately than unfamiliar ones and under difficult viewing conditions when unfamiliar face recognition fails. The neural basis for this fundamental difference remains unknown. Using whole-brain functional magnetic resonance imaging, we found that personally familiar faces engage the macaque face-processing network more than unfamiliar faces. Familiar faces also recruited two hitherto unknown face areas at anatomically conserved locations within the perirhinal cortex and the temporal pole. These two areas, but not the core face-processing network, responded to familiar faces emerging from a blur with a characteristic nonlinear surge, akin to the abruptness of familiar face recognition. In contrast, responses to unfamiliar faces and objects remained linear. Thus, two temporal lobe areas extend the core face-processing network into a familiar face-recognition system. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  9. Brains, innovations, tools and cultural transmission in birds, non-human primates and fossil hominins

    Directory of Open Access Journals (Sweden)

    Louis eLefebvre

    2013-06-01

    Full Text Available Recent work on birds and non-human primates has shown that taxonomic differences in field measures of innovation, tool use and social learning are associated with size of the mammalian cortex and avian mesopallium and nidopallium, as well as ecological traits like colonization success. Here, I review this literature and suggest that many of its findings are relevant to hominin intelligence. In particular, our large brains and increased intelligence may be partly independent of our ape phylogeny and the result of convergent processes similar to those that have moulded avian and platyrrhine intelligence. Tool use, innovativeness and cultural transmission might be linked over our past and in our brains as operations of domain-general intelligence. Finally, colonization of new areas may have accompanied increases in both brain size and innovativeness in hominins as they have in other mammals and in birds, potentially accelerating hominin evolution via behavioral drive.

  10. A dedicated network for social interaction processing in the primate brain.

    Science.gov (United States)

    Sliwa, J; Freiwald, W A

    2017-05-19

    Primate cognition requires interaction processing. Interactions can reveal otherwise hidden properties of intentional agents, such as thoughts and feelings, and of inanimate objects, such as mass and material. Where and how interaction analyses are implemented in the brain is unknown. Using whole-brain functional magnetic resonance imaging in macaque monkeys, we discovered a network centered in the medial and ventrolateral prefrontal cortex that is exclusively engaged in social interaction analysis. Exclusivity of specialization was found for no other function anywhere in the brain. Two additional networks, a parieto-premotor and a temporal one, exhibited both social and physical interaction preference, which, in the temporal lobe, mapped onto a fine-grain pattern of object, body, and face selectivity. Extent and location of a dedicated system for social interaction analysis suggest that this function is an evolutionary forerunner of human mind-reading capabilities. Copyright © 2017, American Association for the Advancement of Science.

  11. Attenuation correction for the large non-human primate brain imaging using microPET

    Science.gov (United States)

    Naidoo-Variawa, S.; Lehnert, W.; Kassiou, M.; Banati, R.; Meikle, S. R.

    2010-04-01

    Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a 57Co transmission point source with a 4% energy window. The optimal energy window for a 68Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for 57Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [18F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass 57Co (4% energy window) or 68Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

  12. Attenuation correction for the large non-human primate brain imaging using microPET

    Energy Technology Data Exchange (ETDEWEB)

    Naidoo-Variawa, S; Lehnert, W; Kassiou, M; Banati, R; Meikle, S R [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia)], E-mail: snai3212@uni.sydney.edu.au

    2010-04-21

    Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a {sup 57}Co transmission point source with a 4% energy window. The optimal energy window for a {sup 68}Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for {sup 57}Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [{sup 18}F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass {sup 57}Co (4% energy window) or {sup 68}Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

  13. Diabetes mellitus accelerates Aβ pathology in brain accompanied by enhanced GAβ generation in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Sachi Okabayashi

    Full Text Available Growing evidence suggests that diabetes mellitus (DM is one of the strongest risk factors for developing Alzheimer's disease (AD. However, it remains unclear why DM accelerates AD pathology. In cynomolgus monkeys older than 25 years, senile plaques (SPs are spontaneously and consistently observed in their brains, and neurofibrillary tangles are present at 32 years of age and older. In laboratory-housed monkeys, obesity is occasionally observed and frequently leads to development of type 2 DM. In the present study, we performed histopathological and biochemical analyses of brain tissue in cynomolgus monkeys with type 2 DM to clarify the relationship between DM and AD pathology. Here, we provide the evidence that DM accelerates Aβ pathology in vivo in nonhuman primates who had not undergone any genetic manipulation. In DM-affected monkey brains, SPs were observed in frontal and temporal lobe cortices, even in monkeys younger than 20 years. Biochemical analyses of brain revealed that the amount of GM1-ganglioside-bound Aβ (GAβ--the endogenous seed for Aβ fibril formation in the brain--was clearly elevated in DM-affected monkeys. Furthermore, the level of Rab GTPases was also significantly increased in the brains of adult monkeys with DM, almost to the same levels as in aged monkeys. Intraneuronal accumulation of enlarged endosomes was also observed in DM-affected monkeys, suggesting that exacerbated endocytic disturbance may underlie the acceleration of Aβ pathology due to DM.

  14. Diabetes mellitus accelerates Aβ pathology in brain accompanied by enhanced GAβ generation in nonhuman primates.

    Science.gov (United States)

    Okabayashi, Sachi; Shimozawa, Nobuhiro; Yasutomi, Yasuhiro; Yanagisawa, Katsuhiko; Kimura, Nobuyuki

    2015-01-01

    Growing evidence suggests that diabetes mellitus (DM) is one of the strongest risk factors for developing Alzheimer's disease (AD). However, it remains unclear why DM accelerates AD pathology. In cynomolgus monkeys older than 25 years, senile plaques (SPs) are spontaneously and consistently observed in their brains, and neurofibrillary tangles are present at 32 years of age and older. In laboratory-housed monkeys, obesity is occasionally observed and frequently leads to development of type 2 DM. In the present study, we performed histopathological and biochemical analyses of brain tissue in cynomolgus monkeys with type 2 DM to clarify the relationship between DM and AD pathology. Here, we provide the evidence that DM accelerates Aβ pathology in vivo in nonhuman primates who had not undergone any genetic manipulation. In DM-affected monkey brains, SPs were observed in frontal and temporal lobe cortices, even in monkeys younger than 20 years. Biochemical analyses of brain revealed that the amount of GM1-ganglioside-bound Aβ (GAβ)--the endogenous seed for Aβ fibril formation in the brain--was clearly elevated in DM-affected monkeys. Furthermore, the level of Rab GTPases was also significantly increased in the brains of adult monkeys with DM, almost to the same levels as in aged monkeys. Intraneuronal accumulation of enlarged endosomes was also observed in DM-affected monkeys, suggesting that exacerbated endocytic disturbance may underlie the acceleration of Aβ pathology due to DM.

  15. Functional divergence of the brain-size regulating gene MCPH1 during primate evolution and the origin of humans

    Science.gov (United States)

    2013-01-01

    Background One of the key genes that regulate human brain size, MCPH1 has evolved under strong Darwinian positive selection during the evolution of primates. During this evolution, the divergence of MCPH1 protein sequences among primates may have caused functional changes that contribute to brain enlargement. Results To test this hypothesis, we used co-immunoprecipitation and reporter gene assays to examine the activating and repressing effects of MCPH1 on a set of its down-stream genes and then compared the functional outcomes of a series of mutant MCPH1 proteins that carry mutations at the human- and great-ape-specific sites. The results demonstrate that the regulatory effects of human MCPH1 and rhesus macaque MCPH1 are different in three of eight down-stream genes tested (p73, cyclinE1 and p14ARF), suggesting a functional divergence of MCPH1 between human and non-human primates. Further analyses of the mutant MCPH1 proteins indicated that most of the human-specific mutations could change the regulatory effects on the down-stream genes. A similar result was also observed for one of the four great-ape-specific mutations. Conclusions Collectively, we propose that during primate evolution in general and human evolution in particular, the divergence of MCPH1 protein sequences under Darwinian positive selection led to functional modifications, providing a possible molecular mechanism of how MCPH1 contributed to brain enlargement during primate evolution and human origin. PMID:23697381

  16. Image-guided convection-enhanced delivery of muscimol to the primate brain

    Science.gov (United States)

    Heiss, John D.; Walbridge, Stuart; Asthagiri, Ashok R.; Lonser, Russell R.

    2009-01-01

    Object Muscimol is a potent γ-aminobutyric acid-A receptor agonist (GABAA) that temporarily and selectively suppresses neurons. Targeted muscimol-suppression of neuronal structures could provide insight into the pathophysiology and treatment of a variety of neurologic disorders. To determine if muscimol delivered to the brain by convection-enhanced delivery (CED) could be monitored using a co-infused surrogate magnetic resonance (MR)-imaging tracer, we perfused the striata of primates with tritiated muscimol and gadolinium-DTPA. Methods Three primates underwent convective co-infusion of 3H-muscimol (0.8 μM) and gadolinium-DTPA (−5 mM) into the bilateral striata. Primates underwent serial MR-imaging during infusion and animals were sacrificed immediately after infusion. Post-mortem quantitative autoradiography and histological analysis was performed. Results MR-imaging revealed that infusate (tritiated muscimol and gadolinium-DTPA) distribution was clearly discernible from the non-infused parenchyma. Real-time MR-imaging of the infusion revealed the precise region of anatomic perfusion in each animal. Imaging analysis during infusion revealed that the distribution volume of infusate linearly increased (R=0.92) with volume of infusion. Overall, the mean (±S.D.) volume of distribution to volume of infusion ratio was 8.2±1.3. Autoradiographic analysis revealed that MR-imaging of gadolinium-DTPA closely correlated with the distribution of 3H-muscimol and precisely estimated its volume of distribution (mean difference in volume of distribution, 7.4%). Quantitative autoradiograms revealed that muscimol was homogeneously distributed over the perfused region in a square-shaped concentration profile. Conclusions Muscimol can be effectively delivered to clinically relevant volumes of the primate brain. Moreover, the distribution of muscimol can be tracked by co-infusion of gadolinium-DTPA using MR-imaging. The ability to accurately monitor and control the anatomic

  17. Analysis of vascular homogeneity and anisotropy on high-resolution primate brain imaging.

    Science.gov (United States)

    Kennel, Pol; Fonta, Caroline; Guibert, Romain; Plouraboué, Franck

    2017-11-01

    Using a systematic investigation of brain blood volume, in high-resolution synchrotron 3D images of microvascular structures within cortical regions of a primate brain, we challenge several basic questions regarding possible vascular bias in high-resolution functional neuroimaging. We present a bilateral comparison of cortical regions, where we analyze relative vascular volume in voxels from 150 to 1000 μm side lengths in the white and grey matter. We show that, if voxel size reaches a scale smaller than 300 µm, the vascular volume can no longer be considered homogeneous, either within one hemisphere or in bilateral comparison between samples. We demonstrate that voxel size influences the comparison between vessel-relative volume distributions depending on the scale considered (i.e., hemisphere, lobe, or sample). Furthermore, we also investigate how voxel anisotropy and orientation can affect the apparent vascular volume, in accordance with actual fMRI voxel sizes. These findings are discussed from the various perspectives of high-resolution brain functional imaging. Hum Brain Mapp 38:5756-5777, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Learning to control a brain-machine interface for reaching and grasping by primates.

    Directory of Open Access Journals (Sweden)

    Jose M Carmena

    2003-11-01

    Full Text Available Reaching and grasping in primates depend on the coordination of neural activity in large frontoparietal ensembles. Here we demonstrate that primates can learn to reach and grasp virtual objects by controlling a robot arm through a closed-loop brain-machine interface (BMIc that uses multiple mathematical models to extract several motor parameters (i.e., hand position, velocity, gripping force, and the EMGs of multiple arm muscles from the electrical activity of frontoparietal neuronal ensembles. As single neurons typically contribute to the encoding of several motor parameters, we observed that high BMIc accuracy required recording from large neuronal ensembles. Continuous BMIc operation by monkeys led to significant improvements in both model predictions and behavioral performance. Using visual feedback, monkeys succeeded in producing robot reach-and-grasp movements even when their arms did not move. Learning to operate the BMIc was paralleled by functional reorganization in multiple cortical areas, suggesting that the dynamic properties of the BMIc were incorporated into motor and sensory cortical representations.

  19. Adeno-associated virus type 6 is retrogradely transported in the non-human primate brain.

    Science.gov (United States)

    San Sebastian, W; Samaranch, L; Heller, G; Kells, A P; Bringas, J; Pivirotto, P; Forsayeth, J; Bankiewicz, K S

    2013-12-01

    We recently demonstrated that axonal transport of adeno-associated virus (AAV) is serotype-dependent. Thus, AAV serotype 2 (AAV2) is anterogradely transported (e.g., from cell bodies to nerve terminals) in both rat and non-human primate (NHP) brain. In contrast, AAV serotype 6 (AAV6) is retrogradely transported from terminals to neuronal cell bodies in the rat brain. However, the directionality of axonal transport of AAV6 in the NHP brain has not been determined. In this study, two Cynomolgus macaques received an infusion of AAV6 harboring green fluorescent protein (GFP) into the striatum (caudate and putamen) by magnetic resonance (MR)-guided convection-enhanced delivery. One month after infusion, immunohistochemical staining of brain sections revealed a striatal GFP expression that corresponded well with MR signal observed during gene delivery. As shown previously in rats, GFP expression was detected throughout the prefrontal, frontal and parietal cortex, as well as the substantia nigra pars compacta and thalamus, indicating retrograde transport of the vector in NHP. AAV6-GFP preferentially transduced neurons, although a few astrocytes were also transduced. Transduction of non-neuronal cells in the brain was associated with the upregulation of the major histocompatibility complex-II and lymphocytic infiltration as previously observed with AAV1 and AAV9. This contrasts with highly specific neuronal transduction in the rat brain. Retrograde axonal transport of AAV6 from a single striatal infusion permits efficient transduction of cortical neurons in significant tissue volumes that otherwise would be difficult to achieve.

  20. Using stereotactic brain atlases for small rodents and nonhuman primates for optrode array customization

    Science.gov (United States)

    Boutte, Ronald W.; Merlin, Sam; Griffiths, Brandon; Parry, Trent; Blair, Steve

    2017-02-01

    As the optogenetic field expands its need to target with high specificity only grows more crucial. This work will show a method for customizing soda-lime glass optrode arrays so that fine structures within the brains of small rodents and nonhuman primates can be optically interrogated below the outer cortical layer. An 8 × 6 array is customized for optrode length (400 μm ), optrode width (75 μm ), optrode pitch (400 μm ), backplane thickness (500 μm ), and overall form factor (3.45 mm × 2.65 mm ). The 400 μm long optrode is capable of illuminating the cortical Layer IV of rhesus macaque ( Macaca Fascicularis ) and the motor cortex of small mice ( Mus Musculus ).

  1. Evolutionary modeling and correcting for observation error support a 3/5 brain-body allometry for primates.

    Science.gov (United States)

    Grabowski, Mark; Voje, Kjetil L; Hansen, Thomas F

    2016-05-01

    The tight brain-body allometry across mammals and primates has motivated and informed many hypotheses about brain evolution in humans and other taxa. While a 2/3 or a 3/4 scaling is often at the core of such research, such exponents are derived from estimates based on particular statistical and evolutionary assumptions without careful consideration of how either may influence findings. Here we quantify primate brain-body allometry using phylogenetic comparative methods based on models of both adaptive and constrained evolution, and estimate and account for observational error in both response and predictor variables. Our results supported an evolutionary model in which brain size is directly constrained to evolve in unison with body size, rather than adapting to changes in the latter. The effects of controlling for phylogeny and observation error were substantial, and our analysis yielded a novel 3/5 scaling exponent for primate brain-body evolutionary allometry. Using this exponent with the latest brain- and body-size estimates to calculate new encephalization quotients for apes, humans, and fossil hominins, we found early hominins were substantially more encephalized than previously thought. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. The effects of chronic alcohol self-administration in nonhuman primate brain networks.

    Science.gov (United States)

    Telesford, Qawi K; Laurienti, Paul J; Davenport, April T; Friedman, David P; Kraft, Robert A; Daunais, James B

    2015-04-01

    Long-term alcohol abuse is associated with change in behavior, brain structure, and brain function. However, the nature of these changes is not well understood. In this study, we used network science to analyze a nonhuman primate model of ethanol self-administration to evaluate functional differences between animals with chronic alcohol use and animals with no exposure to alcohol. Of particular interest was how chronic alcohol exposure may affect the resting state network. Baseline resting state functional magnetic resonance imaging was acquired in a cohort of vervet monkeys. Animals underwent an induction period where they were exposed to an isocaloric maltose dextrin solution (control) or ethanol in escalating doses over three 30-day epochs. Following induction, animals were given ad libitum access to water and a maltose dextrin solution (control) or water and ethanol for 22 h/d over 12 months. Cross-sectional analyses examined region of interests in hubs and community structure across animals to determine differences between drinking and nondrinking animals after the 12-month free access period. Animals were classified as lighter (Animals that consume alcohol show topological differences in brain network organization, particularly in animals that drink heavily. Differences in the resting state network were linked to areas that are associated with spatial association, working memory, and visuomotor processing. Copyright © 2015 by the Research Society on Alcoholism.

  3. The need for calcium imaging in nonhuman primates: New motor neuroscience and brain-machine interfaces.

    Science.gov (United States)

    O'Shea, Daniel J; Trautmann, Eric; Chandrasekaran, Chandramouli; Stavisky, Sergey; Kao, Jonathan C; Sahani, Maneesh; Ryu, Stephen; Deisseroth, Karl; Shenoy, Krishna V

    2017-01-01

    A central goal of neuroscience is to understand how populations of neurons coordinate and cooperate in order to give rise to perception, cognition, and action. Nonhuman primates (NHPs) are an attractive model with which to understand these mechanisms in humans, primarily due to the strong homology of their brains and the cognitively sophisticated behaviors they can be trained to perform. Using electrode recordings, the activity of one to a few hundred individual neurons may be measured electrically, which has enabled many scientific findings and the development of brain-machine interfaces. Despite these successes, electrophysiology samples sparsely from neural populations and provides little information about the genetic identity and spatial micro-organization of recorded neurons. These limitations have spurred the development of all-optical methods for neural circuit interrogation. Fluorescent calcium signals serve as a reporter of neuronal responses, and when combined with post-mortem optical clearing techniques such as CLARITY, provide dense recordings of neuronal populations, spatially organized and annotated with genetic and anatomical information. Here, we advocate that this methodology, which has been of tremendous utility in smaller animal models, can and should be developed for use with NHPs. We review here several of the key opportunities and challenges for calcium-based optical imaging in NHPs. We focus on motor neuroscience and brain-machine interface design as representative domains of opportunity within the larger field of NHP neuroscience. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. A Window into brain development: hdEEG methods to track visual development in nonhuman primates.

    Science.gov (United States)

    Voyles, Angela C; Kiorpes, Lynne

    2016-12-01

    Electroencephalography (EEG) is widely used to study human brain activity, and is a useful tool for bridging the gap between invasive neural recording assays and behavioral data. High-density EEG (hdEEG) methods currently used for human subjects for use with infant macaque monkeys, a species that exhibits similar visual development to humans over a shorter time course was adapted. Unlike monkeys, human subjects were difficult to study longitudinally and were not appropriate for direct within-species comparison to neuronal data. About 27-channel electrode caps, which allowed collection of hdEEG data from infant monkeys across development were designed. Acuity and contrast sweep VEP responses to grating stimuli was obtained and a new method for objective threshold estimation based on response signal-to-noise ratios at different stimulus levels was established. The developmental trajectories of VEP-measured contrast sensitivity and acuity to previously collected behavioral and neuronal data were compared. The VEP measures showed similar rates of development to behavioral measures, both of which were slower than direct neuronal measures; VEP thresholds were higher than other measures. This is the first usage of non-invasive technology in non-human primates. Other means to assess neural sensitivity in infants were all invasive. Use of hdEEG with infant monkeys opens many possibilities for tracking development of vision and other functions in non-human primates, and can expand our understanding of the relationship between neuronal activity and behavioral capabilities across various sensory and cognitive domains. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1342-1359, 2016. © 2016 Wiley Periodicals, Inc.

  5. On the relationships of postcanine tooth size with dietary quality and brain volume in primates: implications for hominin evolution.

    Science.gov (United States)

    Jiménez-Arenas, Juan Manuel; Pérez-Claros, Juan Antonio; Aledo, Juan Carlos; Palmqvist, Paul

    2014-01-01

    Brain volume and cheek-tooth size have traditionally been considered as two traits that show opposite evolutionary trends during the evolution of Homo. As a result, differences in encephalization and molarization among hominins tend to be interpreted in paleobiological grounds, because both traits were presumably linked to the dietary quality of extinct species. Here we show that there is an essential difference between the genus Homo and the living primate species, because postcanine tooth size and brain volume are related to negative allometry in primates and show an inverse relationship in Homo. However, when size effects are removed, the negative relationship between encephalization and molarization holds only for platyrrhines and the genus Homo. In addition, there is no general trend for the relationship between postcanine tooth size and dietary quality among the living primates. If size and phylogeny effects are both removed, this relationship vanishes in many taxonomic groups. As a result, the suggestion that the presence of well-developed postcanine teeth in extinct hominins should be indicative of a poor-quality diet cannot be generalized to all extant and extinct primates.

  6. On the Relationships of Postcanine Tooth Size with Dietary Quality and Brain Volume in Primates: Implications for Hominin Evolution

    Directory of Open Access Journals (Sweden)

    Juan Manuel Jiménez-Arenas

    2014-01-01

    Full Text Available Brain volume and cheek-tooth size have traditionally been considered as two traits that show opposite evolutionary trends during the evolution of Homo. As a result, differences in encephalization and molarization among hominins tend to be interpreted in paleobiological grounds, because both traits were presumably linked to the dietary quality of extinct species. Here we show that there is an essential difference between the genus Homo and the living primate species, because postcanine tooth size and brain volume are related to negative allometry in primates and show an inverse relationship in Homo. However, when size effects are removed, the negative relationship between encephalization and molarization holds only for platyrrhines and the genus Homo. In addition, there is no general trend for the relationship between postcanine tooth size and dietary quality among the living primates. If size and phylogeny effects are both removed, this relationship vanishes in many taxonomic groups. As a result, the suggestion that the presence of well-developed postcanine teeth in extinct hominins should be indicative of a poor-quality diet cannot be generalized to all extant and extinct primates.

  7. On the Relationships of Postcanine Tooth Size with Dietary Quality and Brain Volume in Primates: Implications for Hominin Evolution

    Science.gov (United States)

    Jiménez-Arenas, Juan Manuel; Pérez-Claros, Juan Antonio; Aledo, Juan Carlos; Palmqvist, Paul

    2014-01-01

    Brain volume and cheek-tooth size have traditionally been considered as two traits that show opposite evolutionary trends during the evolution of Homo. As a result, differences in encephalization and molarization among hominins tend to be interpreted in paleobiological grounds, because both traits were presumably linked to the dietary quality of extinct species. Here we show that there is an essential difference between the genus Homo and the living primate species, because postcanine tooth size and brain volume are related to negative allometry in primates and show an inverse relationship in Homo. However, when size effects are removed, the negative relationship between encephalization and molarization holds only for platyrrhines and the genus Homo. In addition, there is no general trend for the relationship between postcanine tooth size and dietary quality among the living primates. If size and phylogeny effects are both removed, this relationship vanishes in many taxonomic groups. As a result, the suggestion that the presence of well-developed postcanine teeth in extinct hominins should be indicative of a poor-quality diet cannot be generalized to all extant and extinct primates. PMID:24592388

  8. Focal Brain Injury Associated with a Model of Severe Hypoxic-Ischemic Encephalopathy in Nonhuman Primates.

    Science.gov (United States)

    McAdams, Ryan M; McPherson, Ronald J; Kapur, Raj P; Juul, Sandra E

    2017-01-01

    Worldwide, hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal mortality and morbidity. To better understand the mechanisms contributing to brain injury and improve outcomes in neonates with HIE, better preclinical animal models that mimic the clinical situation following birth asphyxia in term newborns are needed. In an effort to achieve this goal, we modified our nonhuman primate model of HIE induced by in utero umbilical cord occlusion (UCO) to include postnatal hypoxic episodes, in order to simulate apneic events in human neonates with HIE. We describe a cohort of 4 near-term fetal Macaca nemestrina that underwent 18 min of in utero UCO, followed by cesarean section delivery, resuscitation, and subsequent postnatal mechanical ventilation, with exposure to intermittent daily hypoxia (3 min, 8% O2 3-8 times daily for 3 days). After delivery, all animals demonstrated severe metabolic acidosis (pH 7 ± 0.12; mean ± SD) and low APGAR scores (neonates after severe, abrupt hypoxic-ischemic insults. The UCO model permits timely detection of biomarkers associated with specific patterns of neonatal brain injury, and it may ultimately be useful for validating therapeutic strategies to treat neonatal HIE. © 2017 S. Karger AG, Basel.

  9. The brain's router: a cortical network model of serial processing in the primate brain

    NARCIS (Netherlands)

    Zylberberg, Ariel; Fernández Slezak, Diego; Roelfsema, Pieter R.; Dehaene, Stanislas; Sigman, Mariano

    2010-01-01

    The human brain efficiently solves certain operations such as object recognition and categorization through a massively parallel network of dedicated processors. However, human cognition also relies on the ability to perform an arbitrarily large set of tasks by flexibly recombining different

  10. Faster scaling of visual neurons in cortical areas relative to subcortical structures in non-human primate brains

    OpenAIRE

    Collins, C. E.; Leitch, D. B.; Wong, P.; Kaas, J. H.; Herculano-Houzel, Suzana

    2012-01-01

    Cortical expansion, both in absolute terms and in relation to subcortical structures, is considered a major trend in mammalian brain evolution with important functional implications, given that cortical computations should add complexity and flexibility to information processing. Here, we investigate the numbers of neurons that compose 4 structures in the visual pathway across 11 non-human primate species to determine the scaling relationships that apply to these structures and among them. We...

  11. High-resolution imaging of the large non-human primate brain using microPET: a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Naidoo-Variawa, S [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia); Hey-Cunningham, A J [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia); Lehnert, W [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia); Kench, P L [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia); Kassiou, M [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia); Banati, R [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia); Meikle, S R [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia)

    2007-11-21

    The neuroanatomy and physiology of the baboon brain closely resembles that of the human brain and is well suited for evaluating promising new radioligands in non-human primates by PET and SPECT prior to their use in humans. These studies are commonly performed on clinical scanners with 5 mm spatial resolution at best, resulting in sub-optimal images for quantitative analysis. This study assessed the feasibility of using a microPET animal scanner to image the brains of large non-human primates, i.e. papio hamadryas (baboon) at high resolution. Factors affecting image accuracy, including scatter, attenuation and spatial resolution, were measured under conditions approximating a baboon brain and using different reconstruction strategies. Scatter fraction measured 32% at the centre of a 10 cm diameter phantom. Scatter correction increased image contrast by up to 21% but reduced the signal-to-noise ratio. Volume resolution was superior and more uniform using maximum a posteriori (MAP) reconstructed images (3.2-3.6 mm{sup 3} FWHM from centre to 4 cm offset) compared to both 3D ordered subsets expectation maximization (OSEM) (5.6-8.3 mm{sup 3}) and 3D reprojection (3DRP) (5.9-9.1 mm{sup 3}). A pilot {sup 18}F-2-fluoro-2-deoxy-d-glucose ([{sup 18}F]FDG) scan was performed on a healthy female adult baboon. The pilot study demonstrated the ability to adequately resolve cortical and sub-cortical grey matter structures in the baboon brain and improved contrast when images were corrected for attenuation and scatter and reconstructed by MAP. We conclude that high resolution imaging of the baboon brain with microPET is feasible with appropriate choices of reconstruction strategy and corrections for degrading physical effects. Further work to develop suitable correction algorithms for high-resolution large primate imaging is warranted.

  12. Wireless Cortical Brain-Machine Interface for Whole-Body Navigation in Primates

    Science.gov (United States)

    Rajangam, Sankaranarayani; Tseng, Po-He; Yin, Allen; Lehew, Gary; Schwarz, David; Lebedev, Mikhail A.; Nicolelis, Miguel A. L.

    2016-03-01

    Several groups have developed brain-machine-interfaces (BMIs) that allow primates to use cortical activity to control artificial limbs. Yet, it remains unknown whether cortical ensembles could represent the kinematics of whole-body navigation and be used to operate a BMI that moves a wheelchair continuously in space. Here we show that rhesus monkeys can learn to navigate a robotic wheelchair, using their cortical activity as the main control signal. Two monkeys were chronically implanted with multichannel microelectrode arrays that allowed wireless recordings from ensembles of premotor and sensorimotor cortical neurons. Initially, while monkeys remained seated in the robotic wheelchair, passive navigation was employed to train a linear decoder to extract 2D wheelchair kinematics from cortical activity. Next, monkeys employed the wireless BMI to translate their cortical activity into the robotic wheelchair’s translational and rotational velocities. Over time, monkeys improved their ability to navigate the wheelchair toward the location of a grape reward. The navigation was enacted by populations of cortical neurons tuned to whole-body displacement. During practice with the apparatus, we also noticed the presence of a cortical representation of the distance to reward location. These results demonstrate that intracranial BMIs could restore whole-body mobility to severely paralyzed patients in the future.

  13. Automatic pose correction for image-guided nonhuman primate brain surgery planning

    Science.gov (United States)

    Ghafurian, Soheil; Chen, Antong; Hines, Catherine; Dogdas, Belma; Bone, Ashleigh; Lodge, Kenneth; O'Malley, Stacey; Winkelmann, Christopher T.; Bagchi, Ansuman; Lubbers, Laura S.; Uslaner, Jason M.; Johnson, Colena; Renger, John; Zariwala, Hatim A.

    2016-03-01

    Intracranial delivery of recombinant DNA and neurochemical analysis in nonhuman primate (NHP) requires precise targeting of various brain structures via imaging derived coordinates in stereotactic surgeries. To attain targeting precision, the surgical planning needs to be done on preoperative three dimensional (3D) CT and/or MR images, in which the animals head is fixed in a pose identical to the pose during the stereotactic surgery. The matching of the image to the pose in the stereotactic frame can be done manually by detecting key anatomical landmarks on the 3D MR and CT images such as ear canal and ear bar zero position. This is not only time intensive but also prone to error due to the varying initial poses in the images which affects both the landmark detection and rotation estimation. We have introduced a fast, reproducible, and semi-automatic method to detect the stereotactic coordinate system in the image and correct the pose. The method begins with a rigid registration of the subject images to an atlas and proceeds to detect the anatomical landmarks through a sequence of optimization, deformable and multimodal registration algorithms. The results showed similar precision (maximum difference of 1.71 in average in-plane rotation) to a manual pose correction.

  14. Targeting of deep-brain structures in nonhuman primates using MR and CT Images

    Science.gov (United States)

    Chen, Antong; Hines, Catherine; Dogdas, Belma; Bone, Ashleigh; Lodge, Kenneth; O'Malley, Stacey; Connolly, Brett; Winkelmann, Christopher T.; Bagchi, Ansuman; Lubbers, Laura S.; Uslaner, Jason M.; Johnson, Colena; Renger, John; Zariwala, Hatim A.

    2015-03-01

    In vivo gene delivery in central nervous systems of nonhuman primates (NHP) is an important approach for gene therapy and animal model development of human disease. To achieve a more accurate delivery of genetic probes, precise stereotactic targeting of brain structures is required. However, even with assistance from multi-modality 3D imaging techniques (e.g. MR and CT), the precision of targeting is often challenging due to difficulties in identification of deep brain structures, e.g. the striatum which consists of multiple substructures, and the nucleus basalis of meynert (NBM), which often lack clear boundaries to supporting anatomical landmarks. Here we demonstrate a 3D-image-based intracranial stereotactic approach applied toward reproducible intracranial targeting of bilateral NBM and striatum of rhesus. For the targeting we discuss the feasibility of an atlas-based automatic approach. Delineated originally on a high resolution 3D histology-MR atlas set, the NBM and the striatum could be located on the MR image of a rhesus subject through affine and nonrigid registrations. The atlas-based targeting of NBM was compared with the targeting conducted manually by an experienced neuroscientist. Based on the targeting, the trajectories and entry points for delivering the genetic probes to the targets could be established on the CT images of the subject after rigid registration. The accuracy of the targeting was assessed quantitatively by comparison between NBM locations obtained automatically and manually, and finally demonstrated qualitatively via post mortem analysis of slices that had been labelled via Evan Blue infusion and immunohistochemistry.

  15. Brain mechanisms of acoustic communication in humans and nonhuman primates: an evolutionary perspective.

    Science.gov (United States)

    Ackermann, Hermann; Hage, Steffen R; Ziegler, Wolfram

    2014-12-01

    Any account of "what is special about the human brain" (Passingham 2008) must specify the neural basis of our unique ability to produce speech and delineate how these remarkable motor capabilities could have emerged in our hominin ancestors. Clinical data suggest that the basal ganglia provide a platform for the integration of primate-general mechanisms of acoustic communication with the faculty of articulate speech in humans. Furthermore, neurobiological and paleoanthropological data point at a two-stage model of the phylogenetic evolution of this crucial prerequisite of spoken language: (i) monosynaptic refinement of the projections of motor cortex to the brainstem nuclei that steer laryngeal muscles, presumably, as part of a "phylogenetic trend" associated with increasing brain size during hominin evolution; (ii) subsequent vocal-laryngeal elaboration of cortico-basal ganglia circuitries, driven by human-specific FOXP2 mutations.;>This concept implies vocal continuity of spoken language evolution at the motor level, elucidating the deep entrenchment of articulate speech into a "nonverbal matrix" (Ingold 1994), which is not accounted for by gestural-origin theories. Moreover, it provides a solution to the question for the adaptive value of the "first word" (Bickerton 2009) since even the earliest and most simple verbal utterances must have increased the versatility of vocal displays afforded by the preceding elaboration of monosynaptic corticobulbar tracts, giving rise to enhanced social cooperation and prestige. At the ontogenetic level, the proposed model assumes age-dependent interactions between the basal ganglia and their cortical targets, similar to vocal learning in some songbirds. In this view, the emergence of articulate speech builds on the "renaissance" of an ancient organizational principle and, hence, may represent an example of "evolutionary tinkering" (Jacob 1977).

  16. Different scaling of white matter volume, cortical connectivity, and gyrification across rodent and primate brains

    Science.gov (United States)

    Ventura-Antunes, Lissa; Mota, Bruno; Herculano-Houzel, Suzana

    2013-01-01

    Expansion of the cortical gray matter in evolution has been accompanied by an even faster expansion of the subcortical white matter volume and by folding of the gray matter surface, events traditionally considered to occur homogeneously across mammalian species. Here we investigate how white matter expansion and cortical folding scale across species of rodents and primates as the gray matter gains neurons. We find very different scaling rules of white matter expansion across the two orders, favoring volume conservation and smaller propagation times in primates. For a similar number of cortical neurons, primates have a smaller connectivity fraction and less white matter volume than rodents; moreover, as the cortex gains neurons, there is a much faster increase in white matter volume and in its ratio to gray matter volume in rodents than in primates. Order-specific scaling of the white matter can be attributed to different scaling of average fiber caliber and neuronal connectivity in rodents and primates. Finally, cortical folding increases as different functions of the number of cortical neurons in rodents and primates, scaling faster in the latter than in the former. While the neuronal rules that govern gray and white matter scaling are different across rodents and primates, we find that they can be explained by the same unifying model, with order-specific exponents. The different scaling of the white matter has implications for the scaling of propagation time and computational capacity in evolution, and calls for a reappraisal of developmental models of cortical expansion in evolution. PMID:23576961

  17. Positive selection in ASPM is correlated with cerebral cortex evolution across primates but not with whole-brain size.

    Science.gov (United States)

    Ali, Farhan; Meier, Rudolf

    2008-11-01

    The rapid increase of brain size is a key event in human evolution. Abnormal spindle-like microcephaly associated (ASPM) is discussed as a major candidate gene for explaining the exceptionally large brain in humans but ASPM's role remains controversial. Here we use codon-specific models and a comparative approach to test this candidate gene that was initially identified in Homo-chimp comparisons. We demonstrate that accelerated evolution of ASPM (omega = 4.7) at 16 amino acid sites occurred in 9 primate lineages with major changes in relative cerebral cortex size. However, ASPM's evolution is not correlated with major changes in relative whole-brain or cerebellum sizes. Our results suggest that a single candidate gene such as ASPM can influence a specific component of the brain across large clades through changes in a few amino acid sites. We furthermore illustrate the power of using continuous phenotypic variability across primates to rigorously test candidate genes that have been implicated in the evolution of key human traits.

  18. Lessons Learned on "Scaling Up" of Projects

    Science.gov (United States)

    Viadero, Debra

    2007-01-01

    Having developed a technology-based teaching unit on weather that appeared to work well for middle school students, Nancy Butler Songer and her colleagues at the University of Michigan decided in the late 1990s to take the next logical step in their research program: They scaled up. This article discusses lessons learned by several faculty…

  19. "Scaling Up" Good Practices in Girls' Education

    Science.gov (United States)

    Subrahmanian, Ramya

    2005-01-01

    This publication focuses on strategies for meeting international targets and national goals for universalizing girls' access to, retention in and completion of quality education. This will be done through "scaling up" successful interventions, or components of interventions that can be replicated. UNESCO published this book within the…

  20. Prion immunoreactivity in brain, tonsil, gastrointestinal epithelial cells, and blood and lymph vessels in lemurian zoo primates with spongiform encephalopathy.

    Science.gov (United States)

    Bons, N; Mestre-Frances, N; Guiraud, I; Charnay, Y

    1997-12-01

    We report on two animals of a non-human primate species Eulemur fulvus mayottensis, housed in the local zoo and fed over a number of years with a food containing cattle meat, that developed serious neurological symptoms associated with prion immunoreactivity in brain and various viscera. Microscopy of the brains showed neuronal vacuolation with patchy/perivacuolar immunolabelling with an abnormal isoform of prion protein (IR-PrP), an important characteristic of spongiform encephalopathy. For the first time, we report the presence in the same severely ill animals of IR-PrP in the gastrointestinal tract, detected by immunocytochemistry with mono- and polyclonal antibodies directed against various parts of the PrP. Strong PrP labelling was observed in the epithelial cells lining the pharyngeal and gastrointestinal lumen. The tonsils and the walls of the lymph and blood vessels below the intestinal epithelium were also labelled. There were no such immunoreactions in healthy lemurians killed as controls, i.e. a younger congener of the same species housed under the same conditions, and others belonging to the smaller species Microcebus murinus, reared in the laboratory and never fed on commercial food products containing cattle meat. These results demonstrate a strong PrP accumulation in the brain, the gastrointestinal tract and underlying lymphoreticular structures in these primates living in a zoological park and suffering from a spongiform encephalopathy.

  1. Mapping primary gyrogenesis during fetal development in primate brains: high-resolution in utero structural MRI study of fetal brain development in pregnant baboons

    Directory of Open Access Journals (Sweden)

    Peter Kochunov

    2010-05-01

    Full Text Available The global and regional changes in the fetal cerebral cortex in primates were mapped during primary gyrification (PG; weeks 17-25 of 26 weeks total gestation. Studying pregnant baboons using high-resolution MRI in utero, measurements included cerebral volume, cortical surface area, gyrification index and length and depth of ten primary cortical sulci. Seven normally developing fetuses were imaged in two animals longitudinally and sequentially. We compared these results to those on PG that from the ferret studies and analyzed them in the context of our recent studies of phylogenetics of cerebral gyrification. We observed that in both primates and non-primates, the cerebrum undergoes a very rapid transformation into the gyrencephalic state, subsequently accompanied by an accelerated growth in brain volume and cortical surface area. However, PG trends in baboons exhibited some critical differences from those observed in ferrets. For example, in baboons, the growth along the long (length axis of cortical sulci was unrelated to the growth along the short (depth axis and far outpaced it. Additionally, the correlation between the rate of growth along the short sulcal axis and heritability of sulcal depth was negative and approached significance (r=-0.60;p<.10, while the same trend for long axis was positive and not significant (p=0.3;p=0.40. These findings, in an animal that shares a highly orchestrated pattern of PG with humans, suggest that ontogenic processes that influence changes in sulcal length and depth are diverse and possibly driven by different factors in primates than in non-primates.

  2. Scaling up: Distributed machine learning with cooperation

    Energy Technology Data Exchange (ETDEWEB)

    Provost, F.J. [NYNEX Science & Technology, White Plains, NY (United States); Hennessy, D.N. [Univ. of Pittsburgh, PA (United States)

    1996-12-31

    Machine-learning methods are becoming increasingly popular for automated data analysis. However, standard methods do not scale up to massive scientific and business data sets without expensive hardware. This paper investigates a practical alternative for scaling up: the use of distributed processing to take advantage of the often dormant PCs and workstations available on local networks. Each workstation runs a common rule-learning program on a subset of the data. We first show that for commonly used rule-evaluation criteria, a simple form of cooperation can guarantee that a rule will look good to the set of cooperating learners if and only if it would look good to a single learner operating with the entire data set. We then show how such a system can further capitalize on different perspectives by sharing learned knowledge for significant reduction in search effort. We demonstrate the power of the method by learning from a massive data set taken from the domain of cellular fraud detection. Finally, we provide an overview of other methods for scaling up machine learning.

  3. Transcranial Cavitation Detection in Primates during Blood-Brain Barrier Opening – A Performance Assessment Study

    Science.gov (United States)

    Wu, Shih-Ying; Tung, Yao-Sheng; Marquet, Fabrice; Downs, Matthew Eric; Sanchez, Carlos Sierra; Chen, Cherry Chen; Ferrera, Vincent

    2014-01-01

    Focused ultrasound (FUS) has been shown promise in treating the brain locally and noninvasively. Transcranial passive cavitation detection (PCD) provides methodology of monitoring the treatment in real time, while the skull effects remain a major challenge for its translation to the clinic. In this study, we investigated the sensitivity, reliability, and limitations of PCD through primate (macaque and human) skulls in vitro. The results were further correlated with the in vivo macaque studies including the transcranial PCD calibration and real-time monitoring of BBB opening, with magnetic resonance imaging assessing the opening and safety. The stable cavitation doses using harmonics (SCDh) and ultraharmonics (SCDu), the inertial cavitation dose (ICD), and the cavitation signal-to-noise ratio (SNR) were quantified based on the PCD signals. Results showed that through the macaque skull the pressure threshold for detecting the SCDh remained the same as without the skull in place, while it increased for the SCDu and ICD; through the human skull, it increased for all cavitation doses. The transcranial PCD was found reliable both in vitro and in vivo when the transcranial cavitation SNR exceeded the 1-dB detection limit through the in vitro macaque (attenuation: 4.92 dB/mm) and human (attenuation: 7.33 dB/mm) skull. In addition, using long pulses enabled reliable PCD monitoring and facilitate BBB opening at low pressures. The in vivo results showed that the SCDh became detectable at pressures as low as 100 kPa; the ICD, at 250 kPa while it could occur at lower pressures; the SCDu, at 700 kPa and was less reliable at lower pressures. Real-time monitoring of PCD was further implemented during BBB opening, with successful and safe opening achieved at 250–600 kPa in both the thalamus and the putamen. In conclusion, this study shows that transcranial PCD in macaques in vitro and in vivo as well as humans in vitro is reliable by improving the cavitation SNR beyond the 1-d

  4. The INIA19 template and NeuroMaps atlas for primate brain image parcellation and spatial normalization

    Directory of Open Access Journals (Sweden)

    Torsten eRohlfing

    2012-12-01

    Full Text Available The INIA19 is a new, high-quality template for imaging-based studies of non-human primate brains created from high-resolution T1-weighted magnetic resonance (MR images of 19 rhesus macaque (Macaca mulatta animals. Combined with the comprehensive cortical and subcortical label map of the NeuroMaps atlas, the INIA19 is equally suitable for studies requiring both spatial normalization and atlas label propagation. Population-averaged template images are provided for both the brain and the whole head, to allow alignment of the atlas with both skull-stripped and unstripped data, and thus to facilitate its use for skull stripping of new images. This article describes the construction of the template using freely-available software tools, as well as the template itself, which is being made available to the scientific community (http://nitrc.org/projects/inia19/.

  5. Changes in nonhuman primate brain function following chronic alcohol consumption in previously naïve animals.

    Science.gov (United States)

    Rowland, Jared A; Stapleton-Kotloski, Jennifer R; Alberto, Greg E; Davenport, April T; Kotloski, Robert J; Friedman, David P; Godwin, Dwayne W; Daunais, James B

    2017-08-01

    Chronic alcohol abuse is associated with neurophysiological changes in brain activity; however, these changes are not well localized in humans. Non-human primate models of alcohol abuse enable control over many potential confounding variables associated with human studies. The present study utilized high-resolution magnetoencephalography (MEG) to quantify the effects of chronic EtOH self-administration on resting state (RS) brain function in vervet monkeys. Adolescent male vervet monkeys were trained to self-administer ethanol (n=7) or an isocaloric malto-dextrin solution (n=3). Following training, animals received 12 months of free access to ethanol. Animals then underwent RS magnetoencephalography (MEG) and subsequent power spectral analysis of brain activity at 32 bilateral regions of interest associated with the chronic effects of alcohol use. demonstrate localized changes in brain activity in chronic heavy drinkers, including reduced power in the anterior cingulate cortex, hippocampus, and amygdala as well as increased power in the right medial orbital and parietal areas. The current study is the first demonstration of whole-head MEG acquisition in vervet monkeys. Changes in brain activity were consistent with human electroencephalographic studies; however, MEG was able to extend these findings by localizing the observed changes in power to specific brain regions. These regions are consistent with those previously found to exhibit volume loss following chronic heavy alcohol use. The ability to use MEG to evaluate changes in brain activity following chronic ethanol exposure provides a potentially powerful tool to better understand both the acute and chronic effects of alcohol on brain function. Published by Elsevier B.V.

  6. What makes a frontal area of primate brain the frontal eye field?

    Directory of Open Access Journals (Sweden)

    Pierre ePouget

    2015-05-01

    Full Text Available The frontal eye field region (FEF of the oculomotor pathways has been intensely studied. The primary goal of this review is to illustrate the phylogenetic displacement of the FEF locus in primate species. The locus is arrayed along the arcuate sulcus in monkeys and abuts into the primary motor strip region in humans. The strengths and limitations of the various functional, anatomical and histological methodologies used to identify such regions are also discussed.

  7. The blood-brain barrier is intact after levodopa-induced dyskinesias in parkinsonian primates--evidence from in vivo neuroimaging studies

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Jenkins, Bruce G; Choi, Ji-Kyung

    2009-01-01

    It has been suggested, based on rodent studies, that levodopa (L-dopa) induced dyskinesia is associated with a disrupted blood-brain barrier (BBB). We have investigated BBB integrity with in vivo neuroimaging techniques in six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned primates ...

  8. Scaling up the curvature of mammalian metabolism

    Directory of Open Access Journals (Sweden)

    Juan eBueno

    2014-10-01

    Full Text Available A curvilinear relationship between mammalian metabolic rate and body size on a log-log scale has been adopted in lieu of thelongstanding concept of a 3/4 allometric relationship (Kolokotrones et al. 2010. The central tenet of Metabolic Ecology (ME states that metabolism at the individual level scales-up to drive the ecology of populations, communities and ecosystems. If this tenet is correct, the curvature of metabolism should be perceived in other ecological traits. By analyzing the size scaling allometry of eight different mammalian traits including basal and field metabolic rate, offspring biomass production, ingestion rate, costs of locomotion, life span, population growth rate and population density we show that the curvature affects most ecological rates and

  9. A multi-site array for combined local electrochemistry and electrophysiology in the non-human primate brain.

    Science.gov (United States)

    Disney, Anita A; McKinney, Collin; Grissom, Larry; Lu, Xuekun; Reynolds, John H

    2015-11-30

    Currently, the primary technique employed in circuit-level study of the brain is electrophysiology, recording local field or action potentials (LFPs or APs). However most communication between neurons is chemical and the relationship between electrical activity within neurons and chemical signaling between them is not well understood in vivo, particularly for molecules that signal at least in part by non-synaptic transmission. We describe a multi-contact array and accompanying head stage circuit that together enable concurrent electrophysiological and electrochemical recording. The array is small (<200 μm) and can be assembled into a device of arbitrary length. It is therefore well-suited for use in all major in vivo model systems in neuroscience, including non-human primates where the large brain and need for daily insertion and removal of recording devices places particularly strict demands on design. We present a protocol for array fabrication. We then show that a device built in the manner described can record LFPs and perform enzyme-based amperometric detection of choline in the awake macaque monkey. Comparison with existing methods Existing methods allow single mode (electrophysiology or electrochemistry) recording. This system is designed for concurrent, dual-mode recording. It is also the only system designed explicitly to meet the challenges of recording in non-human primates. Our system offers the possibility for conducting in vivo studies in a range of species that examine the relationship between the electrical activity of neurons and their chemical environment, with exquisite spatial and temporal precision. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Quantification of ethanol methyl (1)H magnetic resonance signal intensity following intravenous ethanol administration in primate brain.

    Science.gov (United States)

    Flory, Graham S; O'Malley, Jean; Grant, Kathleen A; Park, Byung; Kroenke, Christopher D

    2010-03-01

    In vivo(1)H magnetic resonance spectroscopy (MRS) can be used to directly monitor brain ethanol. Previously, studies of human subjects have lead to the suggestion that the ethanol methyl (1)H MRS signal intensity relates to tolerance to ethanol's intoxicating effects. More recently, the ethanol (1)H MRS signal intensity has been recognized to vary between brain gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) due to differences in T(2) within these environments. The methods presented here extend ethanol MRS techniques to non-human primate subjects. Twelve monkeys were administered ethanol while sedated and positioned within a 3T MRI system. Chemical shift imaging (CSI) measurements were performed following intravenous infusion of 1g/kg ethanol. Magnetic resonance imaging (MRI) data were also recorded for each monkey to provide volume fractions of GM, WM, and CSF for each CSI spectrum. To estimate co-variance of ethanol MRS intensity with GM, WM, and CSF volume fractions, the relative contribution of each tissue subtype was determined following corrections for radiofrequency pulse profile non-uniformity, chemical shift artifacts, and differences between the point spread function in the CSI data and the imaging data. The ethanol MRS intensity per unit blood ethanol concentration was found to differ between GM, WM, and CSF. Individual differences in MRS intensity were larger in GM than WM. This methodology demonstrates the feasibility of ethanol MRS experiments and analysis in non-human primate subjects, and suggests GM may be a site of significant variation in ethanol MRS intensity between individuals. Copyright 2009 Elsevier Inc. All rights reserved.

  11. Rapid evolution and copy number variation of primate RHOXF2, an X-linked homeobox gene involved in male reproduction and possibly brain function

    Directory of Open Access Journals (Sweden)

    Zhang Rui

    2011-10-01

    Full Text Available Abstract Background Homeobox genes are the key regulators during development, and they are in general highly conserved with only a few reported cases of rapid evolution. RHOXF2 is an X-linked homeobox gene in primates. It is highly expressed in the testicle and may play an important role in spermatogenesis. As male reproductive system is often the target of natural and/or sexual selection during evolution, in this study, we aim to dissect the pattern of molecular evolution of RHOXF2 in primates and its potential functional consequence. Results We studied sequences and copy number variation of RHOXF2 in humans and 16 nonhuman primate species as well as the expression patterns in human, chimpanzee, white-browed gibbon and rhesus macaque. The gene copy number analysis showed that there had been parallel gene duplications/losses in multiple primate lineages. Our evidence suggests that 11 nonhuman primate species have one RHOXF2 copy, and two copies are present in humans and four Old World monkey species, and at least 6 copies in chimpanzees. Further analysis indicated that the gene duplications in primates had likely been mediated by endogenous retrovirus (ERV sequences flanking the gene regions. In striking contrast to non-human primates, humans appear to have homogenized their two RHOXF2 copies by the ERV-mediated non-allelic recombination mechanism. Coding sequence and phylogenetic analysis suggested multi-lineage strong positive selection on RHOXF2 during primate evolution, especially during the origins of humans and chimpanzees. All the 8 coding region polymorphic sites in human populations are non-synonymous, implying on-going selection. Gene expression analysis demonstrated that besides the preferential expression in the reproductive system, RHOXF2 is also expressed in the brain. The quantitative data suggests expression pattern divergence among primate species. Conclusions RHOXF2 is a fast-evolving homeobox gene in primates. The rapid

  12. Rapid evolution and copy number variation of primate RHOXF2, an X-linked homeobox gene involved in male reproduction and possibly brain function.

    Science.gov (United States)

    Niu, Ao-lei; Wang, Yin-qiu; Zhang, Hui; Liao, Cheng-hong; Wang, Jin-kai; Zhang, Rui; Che, Jun; Su, Bing

    2011-10-12

    Homeobox genes are the key regulators during development, and they are in general highly conserved with only a few reported cases of rapid evolution. RHOXF2 is an X-linked homeobox gene in primates. It is highly expressed in the testicle and may play an important role in spermatogenesis. As male reproductive system is often the target of natural and/or sexual selection during evolution, in this study, we aim to dissect the pattern of molecular evolution of RHOXF2 in primates and its potential functional consequence. We studied sequences and copy number variation of RHOXF2 in humans and 16 nonhuman primate species as well as the expression patterns in human, chimpanzee, white-browed gibbon and rhesus macaque. The gene copy number analysis showed that there had been parallel gene duplications/losses in multiple primate lineages. Our evidence suggests that 11 nonhuman primate species have one RHOXF2 copy, and two copies are present in humans and four Old World monkey species, and at least 6 copies in chimpanzees. Further analysis indicated that the gene duplications in primates had likely been mediated by endogenous retrovirus (ERV) sequences flanking the gene regions. In striking contrast to non-human primates, humans appear to have homogenized their two RHOXF2 copies by the ERV-mediated non-allelic recombination mechanism. Coding sequence and phylogenetic analysis suggested multi-lineage strong positive selection on RHOXF2 during primate evolution, especially during the origins of humans and chimpanzees. All the 8 coding region polymorphic sites in human populations are non-synonymous, implying on-going selection. Gene expression analysis demonstrated that besides the preferential expression in the reproductive system, RHOXF2 is also expressed in the brain. The quantitative data suggests expression pattern divergence among primate species. RHOXF2 is a fast-evolving homeobox gene in primates. The rapid evolution and copy number changes of RHOXF2 had been driven by

  13. Robust modulation of arousal regulation, performance, and frontostriatal activity through central thalamic deep brain stimulation in healthy nonhuman primates

    Science.gov (United States)

    Ryou, Jae-Wook; Wei, Xuefeng F.; Butson, Christopher R.; Schiff, Nicholas D.; Purpura, Keith P.

    2016-01-01

    The central thalamus (CT) is a key component of the brain-wide network underlying arousal regulation and sensory-motor integration during wakefulness in the mammalian brain. Dysfunction of the CT, typically a result of severe brain injury (SBI), leads to long-lasting impairments in arousal regulation and subsequent deficits in cognition. Central thalamic deep brain stimulation (CT-DBS) is proposed as a therapy to reestablish and maintain arousal regulation to improve cognition in select SBI patients. However, a mechanistic understanding of CT-DBS and an optimal method of implementing this promising therapy are unknown. Here we demonstrate in two healthy nonhuman primates (NHPs), Macaca mulatta, that location-specific CT-DBS improves performance in visuomotor tasks and is associated with physiological effects consistent with enhancement of endogenous arousal. Specifically, CT-DBS within the lateral wing of the central lateral nucleus and the surrounding medial dorsal thalamic tegmental tract (DTTm) produces a rapid and robust modulation of performance and arousal, as measured by neuronal activity in the frontal cortex and striatum. Notably, the most robust and reliable behavioral and physiological responses resulted when we implemented a novel method of CT-DBS that orients and shapes the electric field within the DTTm using spatially separated DBS leads. Collectively, our results demonstrate that selective activation within the DTTm of the CT robustly regulates endogenous arousal and enhances cognitive performance in the intact NHP; these findings provide insights into the mechanism of CT-DBS and further support the development of CT-DBS as a therapy for reestablishing arousal regulation to support cognition in SBI patients. PMID:27582298

  14. Visual maps in the adult primate cerebral cortex: some implications for brain development and evolution

    Directory of Open Access Journals (Sweden)

    M.G.P. Rosa

    2002-12-01

    Full Text Available In this paper, the topology of cortical visuotopic maps in adult primates is reviewed, with emphasis on recent studies. The observed visuotopic organisation can be summarised with reference to two basic rules. First, adjacent radial columns in the cortex represent partially overlapping regions of the visual field, irrespective of whether these columns are part of the same or different cortical areas. This primary rule is seldom, if ever, violated. Second, adjacent regions of the visual field tend to be represented in adjacent radial columns of a same area. This rule is not as rigid as the first, as many cortical areas form discontinuous, second-order representations of the visual field. A developmental model based on these physiological observations, and on comparative studies of cortical organisation, is then proposed, in order to explain how a combination of molecular specification steps and activity-driven processes can generate the variety of visuotopic organisations observed in adult cortex.

  15. The development of hand-centred visual representations in the primate brain: a computer modelling study using natural visual scenes.

    Directory of Open Access Journals (Sweden)

    Juan Manuel Galeazzi

    2015-12-01

    Full Text Available Neurons that respond to visual targets in a hand-centred frame of reference have been found within various areas of the primate brain. We investigate how hand-centred visual representations may develop in a neural network model of the primate visual system called VisNet, when the model is trained on images of the hand seen against natural visual scenes. The simulations show how such neurons may develop through a biologically plausible process of unsupervised competitive learning and self-organisation. In an advance on our previous work, the visual scenes consisted of multiple targets presented simultaneously with respect to the hand. Three experiments are presented. First, VisNet was trained with computerized images consisting of a realistic image of a hand and and a variety of natural objects, presented in different textured backgrounds during training. The network was then tested with just one textured object near the hand in order to verify if the output cells were capable of building hand-centered representations with a single localised receptive field. We explain the underlying principles of the statistical decoupling that allows the output cells of the network to develop single localised receptive fields even when the network is trained with multiple objects. In a second simulation we examined how some of the cells with hand-centred receptive fields decreased their shape selectivity and started responding to a localised region of hand-centred space as the number of objects presented in overlapping locations during training increases. Lastly, we explored the same learning principles training the network with natural visual scenes collected by volunteers. These results provide an important step in showing how single, localised, hand-centered receptive fields could emerge under more ecologically realistic visual training conditions.

  16. A novel, primate-specific, brain isoform of KCNH2 impacts cortical physiology, cognition, neuronal repolarization and risk for schizophrenia

    Science.gov (United States)

    Huffaker, Stephen J.; Chen, Jingshan; Nicodemus, Kristin K.; Sambataro, Fabio; Yang, Feng; Mattay, Venkata; Lipska, Barbara K.; Hyde, Thomas M.; Song, Jian; Rujescu, Daniel; Giegling, Ina; Mayilyan, Karine; Proust, Morgan J.; Soghoyan, Armen; Caforio, Grazia; Callicott, Joseph H.; Bertolino, Alessandro; Meyer-Lindenberg, Andreas; Chang, Jay; Ji, Yuanyuan; Egan, Michael F.; Goldberg, Terry E.; Kleinman, Joel E.; Lu, Bai; Weinberger, Daniel R.

    2009-01-01

    Organized neuronal firing is critical for cortical processing and is disrupted in schizophrenia. Using 5’ RACE in human brain, we identified a primate-specific isoform (3.1) of the K+-channel KCNH2 that modulates neuronal firing. KCNH2-3.1 mRNA levels are comparable to KCNH2-1A in brain, but 1000-fold lower in heart. In schizophrenic hippocampus, KCNH2-3.1 expression is 2.5-fold greater than KCNH2-1A. A meta-analysis of 5 clinical samples (367 families, 1158 unrelated cases, 1704 controls) shows association of SNPs in KCNH2 with schizophrenia. Risk-associated alleles predict lower IQ scores and speed of cognitive processing, altered memory-linked fMRI signals, and increased KCNH2-3.1 expression in post-mortem hippocampus. KCNH2-3.1 lacks a domain critical for slow channel deactivation. Overexpression of KCNH2-3.1 in primary cortical neurons induces a rapidly deactivating K+ current and a high-frequency, non-adapting firing pattern. These results identify a novel KCNH2 channel involved in cortical physiology, cognition, and psychosis, providing a potential new psychotherapeutic drug target. PMID:19412172

  17. Blood-Brain Barrier Opening in Behaving Non-Human Primates via Focused Ultrasound with Systemically Administered Microbubbles

    Science.gov (United States)

    Downs, Matthew E.; Buch, Amanda; Karakatsani, Maria Eleni; Konofagou, Elisa E.; Ferrera, Vincent P.

    2015-10-01

    Over the past fifteen years, focused ultrasound coupled with intravenously administered microbubbles (FUS) has been proven an effective, non-invasive technique to open the blood-brain barrier (BBB) in vivo. Here we show that FUS can safely and effectively open the BBB at the basal ganglia and thalamus in alert non-human primates (NHP) while they perform a behavioral task. The BBB was successfully opened in 89% of cases at the targeted brain regions of alert NHP with an average volume of opening 28% larger than prior anesthetized FUS procedures. Safety (lack of edema or microhemorrhage) of FUS was also improved during alert compared to anesthetized procedures. No physiological effects (change in heart rate, motor evoked potentials) were observed during any of the procedures. Furthermore, the application of FUS did not disrupt reaching behavior, but in fact improved performance by decreasing reaction times by 23 ms, and significantly decreasing touch error by 0.76 mm on average.

  18. Toward the Language-Ready Brain: Biological Evolution and Primate Comparisons.

    Science.gov (United States)

    Arbib, Michael A

    2017-02-01

    The approach to language evolution suggested here focuses on three questions: How did the human brain evolve so that humans can develop, use, and acquire languages? How can the evolutionary quest be informed by studying brain, behavior, and social interaction in monkeys, apes, and humans? How can computational modeling advance these studies? I hypothesize that the brain is language ready in that the earliest humans had protolanguages but not languages (i.e., communication systems endowed with rich and open-ended lexicons and grammars supporting a compositional semantics), and that it took cultural evolution to yield societies (a cultural constructed niche) in which language-ready brains could become language-using brains. The mirror system hypothesis is a well-developed example of this approach, but I offer it here not as a closed theory but as an evolving framework for the development and analysis of conflicting subhypotheses in the hope of their eventual integration. I also stress that computational modeling helps us understand the evolving role of mirror neurons, not in and of themselves, but only in their interaction with systems "beyond the mirror." Because a theory of evolution needs a clear characterization of what it is that evolved, I also outline ideas for research in neurolinguistics to complement studies of the evolution of the language-ready brain. A clear challenge is to go beyond models of speech comprehension to include sign language and models of production, and to link language to visuomotor interaction with the physical and social world.

  19. Scatter correction for large non-human primate brain imaging using microPET

    Energy Technology Data Exchange (ETDEWEB)

    Naidoo-Variawa, S; Lehnert, W; Banati, R B; Meikle, S R, E-mail: snai3212@uni.sydney.edu.au [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia)

    2011-04-07

    The baboon is well suited to pre-clinical evaluation of novel radioligands for positron emission tomography (PET). We have previously demonstrated the feasibility of using a high resolution animal PET scanner for this application in the baboon brain. However, the non-homogenous distribution of tissue density within the head may give rise to photon scattering effects that reduce contrast and compromise quantitative accuracy. In this study, we investigated the magnitude and distribution of scatter contributing to the final reconstructed image and its variability throughout the baboon brain using phantoms and Monte Carlo simulated data. The scatter fraction is measured up to 36% at the centre of the brain for a wide energy window (350-650 keV) and 19% for a narrow (450-650 keV) window. We observed less than 3% variation in the scatter fraction throughout the brain and found that scattered events arising from radioactivity outside the field of view contribute less than 1% of measured coincidences. In a contrast phantom, scatter and attenuation correction improved contrast recovery compared with attenuation correction on its own and reduced bias to less than 10% at the expense of the reduced signal-to-noise ratio. We conclude that scatter correction is a necessary step for ensuring high quality measurements of the radiotracer distribution in the baboon brain with a microPET scanner, while it is not necessary to model out of field of view scatter or a spatially variant scatter function.

  20. Cis-regulatory elements in the primate brain: from functional specialization to neurodegeneration

    NARCIS (Netherlands)

    Vermunt, Marit W.

    2017-01-01

    Over the last decade, the noncoding part of the genome has been shown to harbour thousands of cis-regulatory elements, such as enhancers, that activate well-defined gene expression programs. Here, we charted active enhancers in a multiplicity of human brain regions to understand the role of

  1. Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates

    Science.gov (United States)

    The xanthophyll pigments lutein and zeaxanthin cross the blood-retina barrier to preferentially accumulate in the macular region of the neural retina. There they form macular pigment, protecting the retina from blue light damage and oxidative stress. Lutein and zeaxanthin also accumulate in brain t...

  2. SPECT imaging with the serotonin transporter radiotracer [{sup 123}I]p ZIENT in nonhuman primate brain

    Energy Technology Data Exchange (ETDEWEB)

    Cosgrove, Kelly P., E-mail: kelly.cosgrove@yale.ed [Yale University School of Medicine, VA Connecticut HCS (116A6), West Haven, CT 06516 (United States); Staley, Julie K.; Baldwin, Ronald M.; Bois, Frederic [Yale University School of Medicine, VA Connecticut HCS (116A6), West Haven, CT 06516 (United States); Plisson, Christophe [Emory University School of Medicine, Atlanta, GA 30322 (United States); Al-Tikriti, Mohammed S. [Yale University School of Medicine, VA Connecticut HCS (116A6), West Haven, CT 06516 (United States); Seibyl, John P. [Institute for Neurodegenerative Disorders, New Haven, CT 06510 (United States); Goodman, Mark M. [Emory University School of Medicine, Atlanta, GA 30322 (United States); Tamagnan, Gilles D. [Yale University School of Medicine, VA Connecticut HCS (116A6), West Haven, CT 06516 (United States); Institute for Neurodegenerative Disorders, New Haven, CT 06510 (United States)

    2010-07-15

    Introduction: Serotonin dysfunction has been linked to a variety of psychiatric diseases; however, an adequate SPECT radioligand to probe the serotonin transporter system has not been successfully developed. The purpose of this study was to characterize and determine the in vivo selectivity of iodine-123-labeled 2{beta}-carbomethoxy-3{beta}-(4'-((Z)-2-iodoethenyl)phenyl)nortropane, [{sup 123}I]p ZIENT, in nonhuman primate brain. Methods: Two ovariohysterectomized female baboons participated in nine studies (one bolus and eight bolus to constant infusion at a ratio of 9.0 h) to evaluate [{sup 123}I]p ZIENT. To evaluate the selectivity of [{sup 123}I]p ZIENT, the serotonin transporter blockers fenfluramine (1.5, 2.5 mg/kg) and citalopram (5 mg/kg), the dopamine transporter blocker methylphenidate (0.5 mg/kg) and the norepinephrine transporter blocker nisoxetine (1 mg/kg) were given at 8 h post-radiotracer injection. Results: In the bolus to constant infusion studies, equilibrium was established by 4-8 h. [{sup 123}I]p ZIENT was 93% and 90% protein bound in the two baboons and there was no detection of lipophilic radiolabeled metabolites entering the brain. In the high-density serotonin transporter regions (diencephalon and brainstem), fenfluramine and citalopram resulted in 35-71% and 129-151% displacement, respectively, whereas methylphenidate and nisoxetine did not produce significant changes (<10%). Conclusion: These findings suggest that [{sup 123}I]p ZIENT is a favorable compound for in vivo SPECT imaging of serotonin transporters with negligible binding to norepinephrine and dopamine transporters.

  3. Non-human primate skull effects on the cavitation detection threshold of FUS-induced blood-brain barrier opening

    Science.gov (United States)

    Wu, Shih-Ying; Tung, Yao-Sheng; Marquet, Fabrice; Chen, Cherry C.; Konofagou, Elisa E.

    2012-11-01

    Microbubble (MB)-assisted focused ultrasound is a promising technique for delivering drugs to the brain by noninvasively and transiently opening the blood-brain barrier (BBB), and monitoring BBB opening using passive cavitation detection (PCD) is critical in detecting its occurrence, extent as well as assessing its mechanism. One of the main obstacles in achieving those objectives in large animals is the transcranial attenuation. To study the effects, the cavitation response through the in-vitro non-human primate (NHP) skull was investigated. In-house manufactured lipid-shelled MB (medium diameter: 4-5 um) were injected into a 4-mm channel of a phantom below a degassed monkey skull. A hydrophone confocally aligned with the FUS transducer served as PCD during sonication (frequency: 0.50 MHz, peak rarefactional pressures: 0.05-0.60 MPa, pulse length: 100 cycles, PRF: 10 Hz, duration: 2 s) for four cases: water without skull, water with skull, MB without skull and MB with skull. A 5.1-MHz linear-array transducer was also used to monitor the MB disruption. The frequency spectra, spectrograms, stable cavitation dose (SCD) and inertial cavitation dose (ICD) were quantified. Results showed that the onset of stable cavitation and inertial cavitation in the experiments occurred at 50 kPa, and was detectable throught the NHP skull since the both the detection thresholds for stable cavitation and inertial cavitation remained unchanged compared to the non-skull case, and the SCD and ICD acquired transcranially may not adequately represent the true extent of stable and inertial cavitation due to the skull attenuation.

  4. Induced Pluripotent Stem Cell-Derived Neural Cells Survive and Mature in the Nonhuman Primate Brain

    Directory of Open Access Journals (Sweden)

    Marina E. Emborg

    2013-03-01

    Full Text Available The generation of induced pluripotent stem cells (iPSCs opens up the possibility for personalized cell therapy. Here, we show that transplanted autologous rhesus monkey iPSC-derived neural progenitors survive for up to 6 months and differentiate into neurons, astrocytes, and myelinating oligodendrocytes in the brains of MPTP-induced hemiparkinsonian rhesus monkeys with a minimal presence of inflammatory cells and reactive glia. This finding represents a significant step toward personalized regenerative therapies.

  5. MicroRNA-driven developmental remodeling in the brain distinguishes humans from other primates.

    Directory of Open Access Journals (Sweden)

    Mehmet Somel

    2011-12-01

    Full Text Available While multiple studies have reported the accelerated evolution of brain gene expression in the human lineage, the mechanisms underlying such changes are unknown. Here, we address this issue from a developmental perspective, by analyzing mRNA and microRNA (miRNA expression in two brain regions within macaques, chimpanzees, and humans throughout their lifespan. We find that constitutive gene expression divergence (species differences independent of age is comparable between humans and chimpanzees. However, humans display a 3-5 times faster evolutionary rate in divergence of developmental patterns, compared to chimpanzees. Such accelerated evolution of human brain developmental patterns (i cannot be explained by life-history changes among species, (ii is twice as pronounced in the prefrontal cortex than the cerebellum, (iii preferentially affects neuron-related genes, and (iv unlike constitutive divergence does not depend on cis-regulatory changes, but might be driven by human-specific changes in expression of trans-acting regulators. We show that developmental profiles of miRNAs, as well as their target genes, show the fastest rates of human-specific evolutionary change, and using a combination of computational and experimental methods, we identify miR-92a, miR-454, and miR-320b as possible regulators of human-specific neural development. Our results suggest that different mechanisms underlie adaptive and neutral transcriptome divergence, and that changes in the expression of a few key regulators may have been a major driving force behind rapid evolution of the human brain.

  6. Chronic Ethanol Consumption Differentially Alters Gray and White Matter Ethanol 1H Methyl Magnetic Resonance Intensity in the Primate Brain

    Science.gov (United States)

    Kroenke, Christopher D.; Flory, Graham S.; Park, Byung; Shaw, Jessica; Rau, Andrew R.; Grant, Kathleen A.

    2013-01-01

    Background In vivo magnetic resonance spectroscopy (MRS) has previously been used to directly monitor brain ethanol. It has been proposed that the ethanol methyl 1H resonance intensity is larger in ethanol-tolerant individuals than in sensitive individuals. To characterize the relationship between long-term ethanol exposure and the brain ethanol MRS intensity, we present data from a longitudinal experiment conducted using nonhuman primate subjects. Methods In vivo MRS was used to measure the gray matter (GM) and white matter (WM) ethanol methyl 1H MRS intensity in 18 adult male rhesus macaques at four time points throughout the course of a chronic drinking experiment. Time points were prior to ethanol drinking, following a 3-month ethanol induction procedure, and following six, and twelve subsequent months of 22-hours/day of “open access” to ethanol (4% w/v) and water. Results The ethanol methyl 1H MRS intensity, which we observed to be independent of age over the range examined, increased with chronic ethanol exposure in GM and WM. In GM, MRS intensity increased from naive-level following the ethanol induction period (90 g/kg cumulative ethanol intake). In WM, MRS intensity was not significantly different from the ethanol-naïve state until after 6 months of 22-hours free access (110–850 g/kg cumulative intake range). The WM MRS intensity in the ethanol-naive state was positively correlated with future drinking, and the increase in WM MRS intensity was negatively correlated with the amount of ethanol consumed throughout the experiment. Conclusions Chronic exposure to ethanol is associated with brain changes that result in differential increases in ethanol MRS intensity in GM and WM. The ethanol-naïve WM MRS intensity pattern is consistent with its previously proposed relationship to innate tolerance to the intoxicating effects of ethanol. Ethanol-dependent MRS intensity changes in GM required less ethanol exposure than was necessary to produce changes in WM

  7. Further statistical analysis for genome-wide expression evolution in primate brain/liver/fibroblast tissue

    Directory of Open Access Journals (Sweden)

    Gu Jianying

    2004-05-01

    Full Text Available Abstract In spite of only a 1-2 per cent genomic DNA sequence difference, humans and chimpanzees differ considerably in behaviour and cognition. Affymetrix microarray technology provides a novel approach to addressing a long-term debate on whether the difference between humans and chimpanzees results from the alteration of gene expressions. Here, we used several statistical methods (distance method, two-sample t-tests, regularised t-tests, ANOVA and bootstrapping to detect the differential expression pattern between humans and great apes. Our analysis shows that the pattern we observed before is robust against various statistical methods; that is, the pronounced expression changes occurred on the human lineage after the split from chimpanzees, and that the dramatic brain expression alterations in humans may be mainly driven by a set of genes with increased expression (up-regulated rather than decreased expression (down-regulated.

  8. Trait-like brain activity during adolescence predicts anxious temperament in primates.

    Directory of Open Access Journals (Sweden)

    Andrew S Fox

    2008-07-01

    Full Text Available Early theorists (Freud and Darwin speculated that extremely shy children, or those with anxious temperament, were likely to have anxiety problems as adults. More recent studies demonstrate that these children have heightened responses to potentially threatening situations reacting with intense defensive responses that are characterized by behavioral inhibition (BI (inhibited motor behavior and decreased vocalizations and physiological arousal. Confirming the earlier impressions, data now demonstrate that children with this disposition are at increased risk to develop anxiety, depression, and comorbid substance abuse. Additional key features of anxious temperament are that it appears at a young age, it is a stable characteristic of individuals, and even in non-threatening environments it is associated with increased psychic anxiety and somatic tension. To understand the neural underpinnings of anxious temperament, we performed imaging studies with 18-fluoro-deoxyglucose (FDG high-resolution Positron Emission Tomography (PET in young rhesus monkeys. Rhesus monkeys were used because they provide a well validated model of anxious temperament for studies that cannot be performed in human children. Imaging the same animal in stressful and secure contexts, we examined the relation between regional metabolic brain activity and a trait-like measure of anxious temperament that encompasses measures of BI and pituitary-adrenal reactivity. Regardless of context, results demonstrated a trait-like pattern of brain activity (amygdala, bed nucleus of stria terminalis, hippocampus, and periaqueductal gray that is predictive of individual phenotypic differences. Importantly, individuals with extreme anxious temperament also displayed increased activity of this circuit when assessed in the security of their home environment. These findings suggest that increased activity of this circuit early in life mediates the childhood temperamental risk to develop anxiety and

  9. Trait-like brain activity during adolescence predicts anxious temperament in primates.

    Science.gov (United States)

    Fox, Andrew S; Shelton, Steven E; Oakes, Terrence R; Davidson, Richard J; Kalin, Ned H

    2008-07-02

    Early theorists (Freud and Darwin) speculated that extremely shy children, or those with anxious temperament, were likely to have anxiety problems as adults. More recent studies demonstrate that these children have heightened responses to potentially threatening situations reacting with intense defensive responses that are characterized by behavioral inhibition (BI) (inhibited motor behavior and decreased vocalizations) and physiological arousal. Confirming the earlier impressions, data now demonstrate that children with this disposition are at increased risk to develop anxiety, depression, and comorbid substance abuse. Additional key features of anxious temperament are that it appears at a young age, it is a stable characteristic of individuals, and even in non-threatening environments it is associated with increased psychic anxiety and somatic tension. To understand the neural underpinnings of anxious temperament, we performed imaging studies with 18-fluoro-deoxyglucose (FDG) high-resolution Positron Emission Tomography (PET) in young rhesus monkeys. Rhesus monkeys were used because they provide a well validated model of anxious temperament for studies that cannot be performed in human children. Imaging the same animal in stressful and secure contexts, we examined the relation between regional metabolic brain activity and a trait-like measure of anxious temperament that encompasses measures of BI and pituitary-adrenal reactivity. Regardless of context, results demonstrated a trait-like pattern of brain activity (amygdala, bed nucleus of stria terminalis, hippocampus, and periaqueductal gray) that is predictive of individual phenotypic differences. Importantly, individuals with extreme anxious temperament also displayed increased activity of this circuit when assessed in the security of their home environment. These findings suggest that increased activity of this circuit early in life mediates the childhood temperamental risk to develop anxiety and depression. In

  10. Readiness for Change. Scaling-Up Brief. Number 3

    Science.gov (United States)

    Fixsen, Dean L.; Blase, Karen A.; Horner, Rob; Sugai, George

    2009-01-01

    The purpose of this "Brief" is to define the variables a state or large district leadership team may wish to consider as they determine if they are "ready" to invest in the scaling-up of an innovation in education. As defined here, "scaling up" means that at least 60% of the students who could benefit from an innovation have access to that…

  11. Reward optimization in the primate brain: a probabilistic model of decision making under uncertainty.

    Directory of Open Access Journals (Sweden)

    Yanping Huang

    Full Text Available A key problem in neuroscience is understanding how the brain makes decisions under uncertainty. Important insights have been gained using tasks such as the random dots motion discrimination task in which the subject makes decisions based on noisy stimuli. A descriptive model known as the drift diffusion model has previously been used to explain psychometric and reaction time data from such tasks but to fully explain the data, one is forced to make ad-hoc assumptions such as a time-dependent collapsing decision boundary. We show that such assumptions are unnecessary when decision making is viewed within the framework of partially observable Markov decision processes (POMDPs. We propose an alternative model for decision making based on POMDPs. We show that the motion discrimination task reduces to the problems of (1 computing beliefs (posterior distributions over the unknown direction and motion strength from noisy observations in a bayesian manner, and (2 selecting actions based on these beliefs to maximize the expected sum of future rewards. The resulting optimal policy (belief-to-action mapping is shown to be equivalent to a collapsing decision threshold that governs the switch from evidence accumulation to a discrimination decision. We show that the model accounts for both accuracy and reaction time as a function of stimulus strength as well as different speed-accuracy conditions in the random dots task.

  12. EEG potentials associated with artificial grammar learning in the primate brain.

    Science.gov (United States)

    Attaheri, Adam; Kikuchi, Yukiko; Milne, Alice E; Wilson, Benjamin; Alter, Kai; Petkov, Christopher I

    2015-09-01

    Electroencephalography (EEG) has identified human brain potentials elicited by Artificial Grammar (AG) learning paradigms, which present participants with rule-based sequences of stimuli. Nonhuman animals are sensitive to certain AGs; therefore, evaluating which EEG Event Related Potentials (ERPs) are associated with AG learning in nonhuman animals could identify evolutionarily conserved processes. We recorded EEG potentials during an auditory AG learning experiment in two Rhesus macaques. The animals were first exposed to sequences of nonsense words generated by the AG. Then surface-based ERPs were recorded in response to sequences that were 'consistent' with the AG and 'violation' sequences containing illegal transitions. The AG violations strongly modulated an early component, potentially homologous to the Mismatch Negativity (mMMN), a P200 and a late frontal positivity (P500). The macaque P500 is similar in polarity and time of occurrence to a late EEG positivity reported in human AG learning studies but might differ in functional role. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Intraparenchymal ultrasound application and improved distribution of infusate with convection-enhanced delivery in rodent and nonhuman primate brain.

    Science.gov (United States)

    Mano, Yui; Saito, Ryuta; Haga, Yoichi; Matsunaga, Tadao; Zhang, Rong; Chonan, Masashi; Haryu, Shinya; Shoji, Takuhiro; Sato, Aya; Sonoda, Yukihiko; Tsuruoka, Noriko; Nishiyachi, Keisuke; Sumiyoshi, Akira; Nonaka, Hiroi; Kawashima, Ryuta; Tominaga, Teiji

    2016-05-01

    OBJECT Convection-enhanced delivery (CED) is an effective drug delivery method that delivers high concentrations of drugs directly into the targeted lesion beyond the blood-brain barrier. However, the drug distribution attained using CED has not satisfactorily covered the entire targeted lesion in tumors such as glioma. Recently, the efficacy of ultrasound assistance was reported for various drug delivery applications. The authors developed a new ultrasound-facilitated drug delivery (UFD) system that enables the application of ultrasound at the infusion site. The purpose of this study was to demonstrate the efficacy of the UFD system and to examine effective ultrasound profiles. METHODS The authors fabricated a steel bar-based device that generates ultrasound and enables infusion of the aqueous drug from one end of the bar. The volume of distribution (Vd) after infusion of 10 ml of 2% Evans blue dye (EBD) into rodent brain was tested with different frequencies and applied voltages: 252 kHz/30 V; 252 kHz/60 V; 524 kHz/13 V; 524 kHz/30 V; and 524 kHz/60 V. In addition, infusion of 5 mM gadopentetate dimeglumine (Gd-DTPA) was tested with 260 kHz/60 V, the distribution of which was evaluated using a 7-T MRI unit. In a nonhuman primate (Macaca fascicularis) study, 300 μl of 1 mM Gd-DTPA/EBD was infused. The final distribution was evaluated using MRI. Two-sample comparisons were made by Student t-test, and 1-way ANOVA was used for multiple comparisons. Significance was set at p system, the Vds of EBD in the UFD groups were significantly larger than those of the control group. When a frequency of 252 kHz was applied, the Vd of the group in which 60 V was applied was significantly larger than that of the group in which 30 V was used. When a frequency of 524 kHz was applied, the Vd tended to increase with application of a higher voltage; however, the differences were not significant (1-way ANOVA). The Vd of Gd-DTPA was also significantly larger in the UFD group than in the

  14. Long-chain n-3 PUFAs from fish oil enhance resting state brain glucose utilization and reduce anxiety in an adult nonhuman primate, the grey mouse lemur.

    Science.gov (United States)

    Pifferi, Fabien; Dorieux, Olène; Castellano, Christian-Alexandre; Croteau, Etienne; Masson, Marie; Guillermier, Martine; Van Camp, Nadja; Guesnet, Philippe; Alessandri, Jean-Marc; Cunnane, Stephen; Dhenain, Marc; Aujard, Fabienne

    2015-08-01

    Decreased brain content of DHA, the most abundant long-chain n-3 polyunsaturated fatty acid (n-3 LCPUFA) in the brain, is accompanied by severe neurosensorial impairments linked to impaired neurotransmission and impaired brain glucose utilization. In the present study, we hypothesized that increasing n-3 LCPUFA intake at an early age may help to prevent or correct the glucose hypometabolism observed during aging and age-related cognitive decline. The effects of 12 months' supplementation with n-3 LCPUFA on brain glucose utilization assessed by positron emission tomography was tested in young adult mouse lemurs (Microcebus murinus). Cognitive function was tested in parallel in the same animals. Lemurs supplemented with n-3 LCPUFA had higher brain glucose uptake and cerebral metabolic rate of glucose compared with controls in all brain regions. The n-3 LCPUFA-supplemented animals also had higher exploratory activity in an open-field task and lower evidence of anxiety in the Barnes maze. Our results demonstrate for the first time in a nonhuman primate that n-3 LCPUFA supplementation increases brain glucose uptake and metabolism and concomitantly reduces anxiety. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  15. Primate phencyclidine model of schizophrenia: sex-specific effects on cognition, brain derived neurotrophic factor, spine synapses, and dopamine turnover in prefrontal cortex.

    Science.gov (United States)

    Elsworth, John D; Groman, Stephanie M; Jentsch, James D; Leranth, Csaba; Redmond, D Eugene; Kim, Jung D; Diano, Sabrina; Roth, Robert H

    2014-10-31

    Cognitive deficits are a core symptom of schizophrenia, yet they remain particularly resistant to treatment. The model provided by repeatedly exposing adult nonhuman primates to phencyclidine has generated important insights into the neurobiology of these deficits, but it remains possible that administration of this psychotomimetic agent during the pre-adult period, when the dorsolateral prefrontal cortex in human and nonhuman primates is still undergoing significant maturation, may provide a greater understanding of schizophrenia-related cognitive deficits. The effects of repeated phencyclidine treatment on spine synapse number, dopamine turnover and BDNF expression in dorsolateral prefrontal cortex, and working memory accuracy were examined in pre-adult monkeys. One week following phencyclidine treatment, juvenile and adolescent male monkeys demonstrated a greater loss of spine synapses in dorsolateral prefrontal cortex than adult male monkeys. Further studies indicated that in juvenile males, a cognitive deficit existed at 4 weeks following phencyclidine treatment, and this impairment was associated with decreased dopamine turnover, decreased brain derived neurotrophic factor messenger RNA, and a loss of dendritic spine synapses in dorsolateral prefrontal cortex. In contrast, female juvenile monkeys displayed no cognitive deficit at 4 weeks after phencyclidine treatment and no alteration in dopamine turnover or brain derived neurotrophic factor messenger RNA or spine synapse number in dorsolateral prefrontal cortex. In the combined group of male and female juvenile monkeys, significant linear correlations were detected between dopamine turnover, spine synapse number, and cognitive performance. As the incidence of schizophrenia is greater in males than females, these findings support the validity of the juvenile primate phencyclidine model and highlight its potential usefulness in understanding the deficits in dorsolateral prefrontal cortex in schizophrenia and

  16. Knowledge-Guided Robust MRI Brain Extraction for Diverse Large-Scale Neuroimaging Studies on Humans and Non-Human Primates

    Science.gov (United States)

    Wang, Yaping; Nie, Jingxin; Yap, Pew-Thian; Li, Gang; Shi, Feng; Geng, Xiujuan; Guo, Lei; Shen, Dinggang

    2014-01-01

    Accurate and robust brain extraction is a critical step in most neuroimaging analysis pipelines. In particular, for the large-scale multi-site neuroimaging studies involving a significant number of subjects with diverse age and diagnostic groups, accurate and robust extraction of the brain automatically and consistently is highly desirable. In this paper, we introduce population-specific probability maps to guide the brain extraction of diverse subject groups, including both healthy and diseased adult human populations, both developing and aging human populations, as well as non-human primates. Specifically, the proposed method combines an atlas-based approach, for coarse skull-stripping, with a deformable-surface-based approach that is guided by local intensity information and population-specific prior information learned from a set of real brain images for more localized refinement. Comprehensive quantitative evaluations were performed on the diverse large-scale populations of ADNI dataset with over 800 subjects (55∼90 years of age, multi-site, various diagnosis groups), OASIS dataset with over 400 subjects (18∼96 years of age, wide age range, various diagnosis groups), and NIH pediatrics dataset with 150 subjects (5∼18 years of age, multi-site, wide age range as a complementary age group to the adult dataset). The results demonstrate that our method consistently yields the best overall results across almost the entire human life span, with only a single set of parameters. To demonstrate its capability to work on non-human primates, the proposed method is further evaluated using a rhesus macaque dataset with 20 subjects. Quantitative comparisons with popularly used state-of-the-art methods, including BET, Two-pass BET, BET-B, BSE, HWA, ROBEX and AFNI, demonstrate that the proposed method performs favorably with superior performance on all testing datasets, indicating its robustness and effectiveness. PMID:24489639

  17. Knowledge-guided robust MRI brain extraction for diverse large-scale neuroimaging studies on humans and non-human primates.

    Science.gov (United States)

    Wang, Yaping; Nie, Jingxin; Yap, Pew-Thian; Li, Gang; Shi, Feng; Geng, Xiujuan; Guo, Lei; Shen, Dinggang

    2014-01-01

    Accurate and robust brain extraction is a critical step in most neuroimaging analysis pipelines. In particular, for the large-scale multi-site neuroimaging studies involving a significant number of subjects with diverse age and diagnostic groups, accurate and robust extraction of the brain automatically and consistently is highly desirable. In this paper, we introduce population-specific probability maps to guide the brain extraction of diverse subject groups, including both healthy and diseased adult human populations, both developing and aging human populations, as well as non-human primates. Specifically, the proposed method combines an atlas-based approach, for coarse skull-stripping, with a deformable-surface-based approach that is guided by local intensity information and population-specific prior information learned from a set of real brain images for more localized refinement. Comprehensive quantitative evaluations were performed on the diverse large-scale populations of ADNI dataset with over 800 subjects (55 ∼ 90 years of age, multi-site, various diagnosis groups), OASIS dataset with over 400 subjects (18 ∼ 96 years of age, wide age range, various diagnosis groups), and NIH pediatrics dataset with 150 subjects (5 ∼ 18 years of age, multi-site, wide age range as a complementary age group to the adult dataset). The results demonstrate that our method consistently yields the best overall results across almost the entire human life span, with only a single set of parameters. To demonstrate its capability to work on non-human primates, the proposed method is further evaluated using a rhesus macaque dataset with 20 subjects. Quantitative comparisons with popularly used state-of-the-art methods, including BET, Two-pass BET, BET-B, BSE, HWA, ROBEX and AFNI, demonstrate that the proposed method performs favorably with superior performance on all testing datasets, indicating its robustness and effectiveness.

  18. Advances and Practices of Bioprocess Scale-up.

    Science.gov (United States)

    Xia, Jianye; Wang, Guan; Lin, Jihan; Wang, Yonghong; Chu, Ju; Zhuang, Yingping; Zhang, Siliang

    2016-01-01

    : This chapter addresses the update progress in bioprocess engineering. In addition to an overview of the theory of multi-scale analysis for fermentation process, examples of scale-up practice combining microbial physiological parameters with bioreactor fluid dynamics are also described. Furthermore, the methodology for process optimization and bioreactor scale-up by integrating fluid dynamics with biokinetics is highlighted. In addition to a short review of the heterogeneous environment in large-scale bioreactor and its effect, a scale-down strategy for investigating this issue is addressed. Mathematical models and simulation methodology for integrating flow field in the reactor and microbial kinetics response are described. Finally, a comprehensive discussion on the advantages and challenges of the model-driven scale-up method is given at the end of this chapter.

  19. Challenges in Designing and Scaling-up Community Services

    DEFF Research Database (Denmark)

    Morelli, Nicola

    2014-01-01

    hidden or latent resources in neighbourhoods. Both the projects are based on the activities in four pilot locations. They are an application of service design to the public sector that provide interesting insights about designing and scaling up highly localised and personalised services and platforms...... several important differences can also be found, that challenge the way those platforms should be designed and scaled up in different contexts. Being at a more advanced stage, the Life 2.0 project obviously provided more insights, whereas MyN gives an opportunity to verify the hypotheses coming from Life...

  20. Social buffering of stress responses in nonhuman primates: Maternal regulation of the development of emotional regulatory brain circuits.

    Science.gov (United States)

    Sanchez, Mar M; McCormack, Kai M; Howell, Brittany R

    2015-01-01

    Social buffering, the phenomenon by which the presence of a familiar individual reduces or even eliminates stress- and fear-induced responses, exists in different animal species and has been examined in the context of the mother-infant relationship, in addition to adults. Although it is a well-known effect, the biological mechanisms that underlie it as well as its developmental impact are not well understood. Here, we provide a review of evidence of social and maternal buffering of stress reactivity in nonhuman primates, and some data from our group suggesting that when the mother-infant relationship is disrupted, maternal buffering is impaired. This evidence underscores the critical role that maternal care plays for proper regulation and development of emotional and stress responses of primate infants. Disruptions of the parent-infant bond constitute early adverse experiences associated with increased risk for psychopathology. We will focus on infant maltreatment, a devastating experience not only for humans, but for nonhuman primates as well. Taking advantage of this naturalistic animal model of adverse maternal caregiving, we have shown that competent maternal care is critical for the development of healthy attachment, social behavior, and emotional and stress regulation, as well as of the neural circuits underlying these functions.

  1. Targeting accuracy and closing timeline of the microbubble-enhanced focused ultrasound blood-brain barrier opening in non-human primates

    Science.gov (United States)

    Marquet, Fabrice; Tung, Yao-Sheng; Teichert, Tobias; Wu, Shih-Ying; Wang, Shutao; Downs, Matthew; Ferrera, Vincent P.; Konofagou, Elisa E.

    2012-11-01

    The delivery of drugs to specific neural targets faces two fundamental problems: Most drugs do not cross the blood-brain barrier and those that do spread to all parts of the brain. To date there exists only one non-invasive methodology with the potential to solve these problems: selective blood-brain barrier disruption using micro-bubble enhanced focused ultrasound. We have recently developed a single-element 500 kHz spherical transducer ultrasound setup for use in the non-human primate. Using this system for selective blood-brain barrier disruption is technically no more challenging than positioning a TMS coil, and does not rely on MRI-guided targeting or expensive phased array ultrasound systems. So far, however, the targeting accuracy that can be achieved with this system has not been quantified systematically. Here we tested the accuracy of the system by targeting the caudate nucleus of the basal ganglia in two macaque monkeys. Our results show that average in-plane error of the system is on the order of 2 mm and targeting error in depth, i.e., along the ultrasound path, is even smaller and averaged 1.2 mm. In summary, targeting accuracy of our system is good enough to enable the selective delivery of drugs to specific sub-structures of the basal ganglia.

  2. Harnessing ICTs to scale-up agricultural innovations | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Agricultural research organizations, governments, and civil society are increasingly looking at how to successfully scale up agriculture and food security innovations to bring more lasting benefits to more people. Information and communication technologies (ICTs) can play an important role in greater uptake of innovations: ...

  3. ORIGINAL ARTICLES Financial and economic costs of scaling up ...

    African Journals Online (AJOL)

    targeted provision of HAART to health care workers may be unavoidable if HAART scale-up plans in ... of knowledge on the cost of providing HAART in resource- constrained settings. Background. Data were ..... absenteeism, reduced productivity, vacancies and inexperience of replacement employees. This study does not ...

  4. Scaling-up Sustainable Aquaculture Development in Sri Lanka ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Scaling-up Sustainable Aquaculture Development in Sri Lanka. The Government of Sri Lanka is increasingly emphasizing aquaculture development as a means to foster rural development, alleviate poverty, and increase food security. A two-year IDRC-funded project identified challenges to the sustainable management of ...

  5. Challenges in Designing and Scaling up Community Services

    DEFF Research Database (Denmark)

    Morelli, Nicola

    2015-01-01

    of the latter is to develop a platform to activate hidden or latent resources in neighbourhoods. Both of the projects are an application of service design to the public sector and together provide useful insights about designing and scaling up highly localized and personalized services and service platforms...

  6. Empirical research methods for technology validation: Scaling up to practice

    NARCIS (Netherlands)

    Wieringa, Roelf J.

    tBefore technology is transferred to the market, it must be validated empirically by simulating future prac-tical use of the technology. Technology prototypes are first investigated in simplified contexts, and thesesimulations are scaled up to conditions of practice step by step as more becomes

  7. Millions Learning: Scaling up Quality Education in Developing Countries

    Science.gov (United States)

    Robinson, Jenny Perlman; Winthrop, Rebecca

    2016-01-01

    "Millions Learning: Scaling up Quality Education in Developing Countries" tells the story of where and how quality education has scaled in low- and middle-income countries. The story emerges from wide-ranging research on scaling and learning, including 14 in-depth case studies from around the globe. Ultimately, "Millions…

  8. Scaling up Prevention of Mother to Child Transmission of HIV ...

    African Journals Online (AJOL)

    Nigeria is scaling up prevention of mother-to-child transmission (PMTCT) of HIV interventions to primary health care centres (PHCs). This retrospective study of PMTCT was at two PHCs in Northwest Nigeria with the main outcome measure being HIV infection rate of exposed infants at 6 weeks of life. Of 10,289 women who ...

  9. New tuberculosis technologies: challenges for retooling and scale-up.

    Science.gov (United States)

    Pai, M; Palamountain, K M

    2012-10-01

    The availability of new tools does not mean that they will be adopted, used correctly, scaled up or have public health impact. Experience to date with new diagnostics suggests that many national tuberculosis programmes (NTPs) in high-burden countries are reluctant to adopt and scale up new tools, even when these are backed by evidence and global policy recommendations. We suggest that there are several common barriers to effective national adoption and scale-up of new technologies: global policy recommendations that do not provide sufficient information for scale-up, complex decision-making processes and weak political commitment at the country level, limited engagement of and support to NTP managers, high cost of tools and poor fit with user needs, unregulated markets and inadequate business models, limited capacity for laboratory strengthening and implementation research, and insufficient advocacy and donor support. Overcoming these barriers will require enhanced country-level advocacy, resources, technical assistance and political commitment. Some of the BRICS (Brazil, Russia, India, China, South Africa) countries are emerging as early adopters of policies and technologies, and are increasing their investments in TB control. They may provide the first opportunities to fully assess the public health impact of new tools.

  10. Scaling up agroforestry farming systems: Lessons from the Malawi ...

    African Journals Online (AJOL)

    The study examined the factors affecting agroforestry technology upscaling and identified gaps in scaling up approaches of agroforestry technologies. One hundred and sixty-four farmers in Malawi Agroforestry Extension (MAFE) project districts of Mzimba, Ntcheu and Mangochi were interviewed. Logistic model was used in ...

  11. Scaling up: Expanding the impact of food security and nutrition ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Corey Piccioni

    innovations; and local knowledge combined with cutting- edge science. The experience of IDRC shows that a portfolio approach provides flexibility to test multiple solutions, and to focus on scaling up the solutions with the highest potential for impact. Building leadership. IDRC strengthens the capacities of researchers, ...

  12. Key considerations in scaling up male circumcision in Tanzania ...

    African Journals Online (AJOL)

    Background. Male circumcision (MC) reduces the risk of sexually transmitted infections (STI) including HIV. The WHO and UNAIDS recommend male circumcision as an additional intervention to prevent HIV infection. Tanzania is embarking on activities to scale up safe male circumcision for HIV prevention and other related ...

  13. Scaling up Intermittent Rice Irrigation for Malaria Control on the ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Scaling up Intermittent Rice Irrigation for Malaria Control on the North Coast of Peru. New research aims to help control malaria in one watershed in northern Peru. Malaria is widespread in Peru's arid North Coast because of the extensive irrigation required to support rice paddies. Rice growing in the region accounts for ...

  14. Scaling up Prevention of Mother to Child Transmission of HIV ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    Jigawa State, 3Federal Medical Centre Katsina, Katsina State.4Takai Comprehensive Health Centre, Takai, Kano State. 5Maternal ... Nigeria is scaling up prevention of mother-to-child transmission (PMTCT) of HIV interventions to primary health care centres. (PHCs). ..... stigma, inability to afford transport cost and long.

  15. Collaborative Group Learning using the SCALE-UP Pedagogy

    Science.gov (United States)

    Feldman, Gerald

    2011-10-01

    The time-honored conventional lecture (``teaching by telling'') has been shown to be an ineffective mode of instruction for science classes. In these cases, where the enhancement of critical thinking skills and the development of problem-solving abilities are emphasized, collaborative group learning environments have proven to be far more effective. In addition, students naturally improve their teamwork skills through the close interaction they have with their group members. Early work on the Studio Physics model at Rensselaer Polytechnic Institute in the mid-1990's was extended to large classes via the SCALE-UP model pioneered at North Carolina State University a few years later. In SCALE-UP, students sit at large round tables in three groups of three --- in this configuration, they carry out a variety of pencil/paper exercises (ponderables) using small whiteboards and perform hands-on activities like demos and labs (tangibles) throughout the class period. They also work on computer simulations using a shared laptop for each group of three. Formal lecture is reduced to a minimal level and the instructor serves more as a ``coach'' to facilitate the academic ``drills'' that the students are working on. Since its inception in 1997, the SCALE-UP pedagogical approach has been adopted by over 100 institutions across the country and about 20 more around the world. In this talk, I will present an overview of the SCALE-UP concept and I will outline the details of its deployment at George Washington University over the past 4 years. I will also discuss empirical data from assessments given to the SCALE-UP collaborative classes and the regular lecture classes at GWU in order to make a comparative study of the effectiveness of the two methodologies.

  16. Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates.

    Science.gov (United States)

    Asad, Abu Bakar Ali; Seah, Stephanie; Baumgartner, Richard; Feng, Dai; Jensen, Andres; Manigbas, Elaine; Henry, Brian; Houghton, Andrea; Evelhoch, Jeffrey L; Derbyshire, Stuart W G; Chin, Chih-Liang

    2016-01-01

    Approximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored. Here we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8). BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle) at baseline and 30 min post-capsaicin (0.1 mg, topical, forearm) application. Tail withdrawal behavioral studies were also conducted in the same animals using 42°C or 48°C water bath pre- and post- capsaicin application (0.1 mg, subcutaneous, tail). Group comparisons between pre- and post-capsaicin application revealed significant BOLD signal increases in brain regions associated with the 'pain matrix', including somatosensory, frontal, and cingulate cortices, as well as the cerebellum (paired t-test, pinduced reduction of latency at both temperatures. These findings provide insights into the specific brain regions involved with aversive, 'pain-like', responses in a nonhuman primate model. Future studies may employ both behavioral and fMRI measures as translational biomarkers to gain deeper understanding of pain processing and evaluate the preclinical efficacy of novel analgesics.

  17. Considerations for Scale-Up of Ferronickel Electric Smelting Furnaces

    Science.gov (United States)

    Hundermark, R. J.; Nelson, L. R.

    2017-02-01

    In ferronickel smelting, the selective carbothermic reduction of calcined nickel laterite ores in large electric furnaces yields a crude ferronickel product. The optimal process for nickel laterite smelting requires a fine balance between the metallurgical requirements of the process (feed composition, nickel recovery, energy consumption, product quality) and the capabilities of the feeding, tapping and off-gas systems, and especially of the furnace crucible and electrical system. The scale-up of nickel laterite smelting operations over the last 50 years has seen a tenfold increase in furnace power input. Furnace operations within the industry are examined to identify common trends and some new metrics are proposed which incorporate the combination of electrode power densities and the impact of alloy nickel grade on gas generation rates, and hence local electrode gas fluxes, which may impact on future scale-up of ferronickel furnaces.

  18. Breastfeeding peer counseling: from efficacy through scale-up.

    Science.gov (United States)

    Chapman, Donna J; Morel, Katherine; Anderson, Alex Kojo; Damio, Grace; Pérez-Escamilla, Rafael

    2010-08-01

    An increasing number of publications have evaluated various breastfeeding peer counseling models. This article describes a systematic review of (a) the randomized trials assessing the effectiveness of breastfeeding peer counseling in improving rates of breastfeeding initiation, duration, exclusivity, and maternal and child health outcomes and (b) scientific literature describing the scale-up of breastfeeding peer counseling programs. Twenty-six peer-reviewed publications were included in this review. The overwhelming majority of evidence from randomized controlled trials evaluating breastfeeding peer counseling indicates that peer counselors effectively improve rates of breastfeeding initiation, duration, and exclusivity. Peer counseling interventions were also shown to significantly decrease the incidence of infant diarrhea and significantly increase the duration of lactational amenorrhea. Breastfeeding peer counseling initiatives are effective and can be scaled up in both developed and developing countries as part of well-coordinated national breastfeeding promotion or maternal-child health programs.

  19. Breastfeeding Peer Counseling: From Efficacy through Scale-up

    OpenAIRE

    Chapman, Donna J.; Morel, Katherine; Anderson, Alex Kojo; Damio, Grace; Pérez-Escamilla, Rafael

    2010-01-01

    There are a growing number of publications evaluating various breastfeeding peer counseling (PC) models. We have systematically reviewed a) the randomized trials assessing the effectiveness of breastfeeding PC in improving rates of breastfeeding initiation, duration, exclusivity and maternal and child health outcomes; and b) scientific literature describing the scale-up of breastfeeding PC programs. Twenty-six peer-reviewed publications were included in this review. The overwhelming majority ...

  20. Processing of sub- and supra-second intervals in the primate brain results from the calibration of neuronal oscillators via sensory, motor and feedback processes

    Directory of Open Access Journals (Sweden)

    Daya Shankar Gupta

    2014-08-01

    Full Text Available The processing of time intervals in the sub- to supra-second range by the brain is critical for the interaction of primates with their surroundings in activities, such as foraging and hunting. For an accurate processing of time intervals by the brain, representation of the physical time within neuronal circuits is necessary. I propose that time-dimension of the physical surrounding is represented in the brain by different types of neuronal oscillators, generating spikes or spike bursts at regular intervals. The proposed oscillators include the pacemaker neurons, tonic inputs and synchronized excitation and inhibition of inter-connected neurons. Oscillators, which are built inside various circuits of brain, help to form modular clocks, processing time intervals or other temporal characteristics specific to functions of a circuit. Relative or absolute duration is represented within neuronal oscillators by ‘neural temporal unit’, defined as the interval between regularly occurring spikes or spike bursts. Oscillator output is processed to produce changes in activities of neurons, named frequency modulator neuron, wired within a separate module, represented by the rate of change in frequency, and frequency of activities, proposed to encode time intervals. Inbuilt oscillators are calibrated by (a feedback processes (b input of time intervals resulting from rhythmic external sensory stimulation and (c synchronous effects of feedback processes and evoked sensory activity. A single active clock is proposed per circuit, which is calibrated by one or more mechanisms. Multiple calibration mechanisms, inbuilt oscillators and the presence of modular connections prevent a complete loss of interval timing functions of the brain.

  1. Testing The Scale-up Approach To Introductory Astronomy

    Science.gov (United States)

    Kregenow, Julia M.; Keller, L.; Rogers, M.; Romero, D.

    2008-09-01

    Ithaca College physics department has begun transforming our general education astronomy courses into hands-on, active-learning courses from the previous lecture-based format. We are using the SCALE-UP model (Student Centered Activities for Large Enrollment University Programs) pioneered at North Carolina State University. Expanding on the successes of Studio Physics (developed at RPI), which exchanges traditionally separate lecture/recitation/ laboratory sessions for one dynamic, active-learning environment for approximately 40 students, SCALE-UP extends this model to accommodate 100+ students by using large round tables creating naturally smaller groups of students. Classes meet three times per week with each class blending lecture, hands-on activities, group problem solving, and the use of student polling devices. We are testing whether this mode of teaching astronomy will lead to a better understanding of astronomy and the nature of science. Applying this approach in both the SCALE-UP classroom (90 students) and a traditional lecture classroom (45 students) in spring 2008, we report on our early results and lessons learned after one semester. We also discuss some of our lingering implementation questions and issues, such as: whether to use the same or different instructor in two parallel sections, requiring textbook reading, reading quizzes, on-line homework and activities, how much math to include, development of hands-on activities, and culling the typically overpacked intro astronomy syllabus.

  2. Three-dimensional histological imaging of primate brain and correlation with in vivo medical device images Imagerie histologique tri-dimensionnelle du cerveau de primate et corrélation avec l'imagerie médicale in vivo

    Directory of Open Access Journals (Sweden)

    Julien Dauguet

    2011-02-01

    Full Text Available The 3D reconstruction of series of histological slices is an imaging technique that appeared about 25 years ago but that is only starting now to become recognized as an imaging modality per se. Thanks to this technique, it becomes possible to restore the spatial consistency of the brain and to match accurately histological slices with an in vivo medical device image such as an MRI or a PET scan. This is of high interest since it allows direct comparison between the histology, often considered as the gold standard in terms of information, and the same medical devices used in clinical routine to image human patients. Thanks to the similarity of their brain with humans and the disease models widely developed for them, non-human primates are privileged species to benefit from this possibility of 3D analysis and in vivo - post mortem correlation. We present in this article a state of the art review of the main techniques proposed to achieve this original imaging technique, followed by a set of some particularly promising neuroimaging applications.La reconstruction 3D de séries de coupes histologiques est une technique d'imagerie qui est apparue il y a 25 ans environ mais qui commence seulement à être reconnue comme une modalité d'imagerie à part entière. Grâce à cette technique, la cohérence 3D du cerveau est rétablie et il devient notamment possible de mettre en correspondance précisément des coupes histologiques avec un examen issu d'un imageur médical comme une IRM ou une TEP. C'est d'un intérêt majeur car cela permet une comparaison directe entre l'histologie, souvent considérée comme la référence étalon en termes d'information fournie, et les mêmes imageurs médicaux que ceux utilisés en routine clinique pour suivre les patients humains. Grâce à leur similarité avec les humains et aux nombreux modèles animaux de maladies développés pour eux, les primates non-humains sont une espèce privilégiée pour bénéficier de

  3. [{sup 18}F]DPA-714 PET imaging of translocator protein TSPO (18 kDa) in the normal and excitotoxically-lesioned nonhuman primate brain

    Energy Technology Data Exchange (ETDEWEB)

    Lavisse, S.; Inoue, K.; Jan, C.; Petit, F.; Dauguet, J.; Guillermier, M.; Rbah-Vidal, L.; Van Camp, N.; Aron-Badin, R.; Hantraye, P. [CEA, I2BM, MIRCen, Fontenay-aux-Roses (France); CEA, CNRS, URA2210, Fontenay-aux-Roses (France); Peyronneau, M.A.; Goutal, S.; Dolle, F. [CEA, I2BM, Service Hospitalier Frederic Joliot, Orsay (France); Remy, P. [CEA, I2BM, MIRCen, Fontenay-aux-Roses (France); CEA, CNRS, URA2210, Fontenay-aux-Roses (France); Service de Neurologie, CHU Henri Mondor, Creteil (France)

    2014-12-09

    We aimed to characterize pharmacologically the TSPO- radioligand [{sup 18}F]DPA-714 in the brain of healthy cynomolgus monkeys and evaluate the cellular origin of its binding in a model of neurodegeneration induced by intrastriatal injection of quinolinic acid (QA). [{sup 18}F]DPA-714 PET images were acquired before and at 2, 7, 14, 21, 49, 70, 91 days after putaminal lesioning. Blocking and displacement studies were carried out (PK11195). Different modelling approaches estimated rate constants and V{sub T} (total distribution volume) which was used to measure longitudinal changes in the lesioned putamen. Sections for immunohistochemical labelling were prepared at the same time-points to evaluate correlations between in vivo [{sup 18}F]DPA-714 binding and microglial/astrocytic activation. [{sup 18}F]DPA-714 showed a widespread distribution with a higher signal in the thalamus and occipital cortex and lower binding in the cerebellum. TSPO was expressed throughout the whole brain and about 73 % of [{sup 18}F]DPA-714 binding was specific for TSPO in vivo. The one-tissue compartment model (1-TCM) provided good and reproducible estimates of V{sub T} and rate constants, and V{sub T} values from the 1-TCM and the Logan approach were highly correlated (r {sup 2} = 0.85). QA lesioning induced an increase in V{sub T}, which was +17 %, +54 %, +157 % and +39 % higher than baseline on days 7, 14, 21 and 91 after QA injection, respectively. Immunohistochemistry revealed an early microglial and a delayed astrocytic activation after QA injection. [{sup 18}F]DPA-714 binding matched TSPO immunopositive areas and showed a stronger colocalization with CD68 microglia than with GFAP-activated astrocytes. [{sup 18}F]DPA-714 binds to TSPO with high specificity in the primate brain under normal conditions and in the QA model. This tracer provides a sensitive tool for assessing neuroinflammation in the human brain. (orig.)

  4. Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington's disease.

    Science.gov (United States)

    Hadaczek, Piotr; Stanek, Lisa; Ciesielska, Agnieszka; Sudhakar, Vivek; Samaranch, Lluis; Pivirotto, Philip; Bringas, John; O'Riordan, Catherine; Mastis, Bryan; San Sebastian, Waldy; Forsayeth, John; Cheng, Seng H; Bankiewicz, Krystof S; Shihabuddin, Lamya S

    2016-01-01

    Huntington's disease (HD) is caused by a toxic gain-of-function associated with the expression of the mutant huntingtin (htt) protein. Therefore, the use of RNA interference to inhibit Htt expression could represent a disease-modifying therapy. The potential of two recombinant adeno-associated viral vectors (AAV), AAV1 and AAV2, to transduce the cortico-striatal tissues that are predominantly affected in HD was explored. Green fluorescent protein was used as a reporter in each vector to show that both serotypes were broadly distributed in medium spiny neurons in the striatum and cortico-striatal neurons after infusion into the putamen and caudate nucleus of nonhuman primates (NHP), with AAV1-directed expression being slightly more robust than AAV2-driven expression. This study suggests that both serotypes are capable of targeting neurons that degenerate in HD, and it sets the stage for the advanced preclinical evaluation of an RNAi-based therapy for this disease.

  5. Barriers and Facilitators to Scaling Up Outpatient Palliative Care.

    Science.gov (United States)

    Bekelman, David B; Rabin, Borsika A; Nowels, Carolyn T; Sahay, Anju; Heidenreich, Paul A; Fischer, Stacy M; Main, Deborah S

    2016-04-01

    The Institute of Medicine recommends people with serious advanced illness have access to skilled palliative care. However, the predominant delivery model of nonhospice palliative care is inpatient, consultative care focused on the end of life, with a small specialist palliative care workforce. The study objective was to understand organizational factors that could influence the adoption and scale-up of outpatient palliative care in chronic advanced illness, using the example of heart failure. This was a cross-sectional qualitative study. Participants were 17 health care providers and local, regional, and national health system leaders from the Veterans Health Administration (VHA) who were considering whether and how to adopt and sustain outpatient palliative care. Individual interviews using semistructured questions assessed domains of the Consolidated Framework for Implementation Science. Most providers and leaders perceived outpatient palliative care as high priority in the VHA given its patient-centeredness and potential to decrease health care use and costs associated with conditions like heart failure. They also supported a collaborative care team model of outpatient palliative care delivery where a palliative care specialist collaborates with medical nurses and social workers. They reported lack of performance measures/incentives for patient-centered care processes and outcomes as a potential barrier to implementation. Features of outpatient palliative care viewed as important for successful adoption and scale-up included coordination and communication with other providers, ease of integration into existing programs, and evidence of improving quality of care while not substantially increasing overall health care costs. Incentives such as performance measures and collaboration with local VHA providers and leaders could improve adoption and scale-up of outpatient palliative care.

  6. Scale-up on electrokinetic remediation: Engineering and technological parameters

    Energy Technology Data Exchange (ETDEWEB)

    López-Vizcaíno, Rubén [Department of Chemical Engineering, Institute of Chemical & Environmental Technologies, University of Castilla-La Mancha, Campus Universitario s/n, 13071 Ciudad Real (Spain); Navarro, Vicente; León, María J. [Geoenvironmental Group, Civil Engineering School, University of Castilla-La Mancha, Avda. Camilo José Cela s/n, 13071 Ciudad Real (Spain); Risco, Carolina [Department of Chemical Engineering, Institute of Chemical & Environmental Technologies, University of Castilla-La Mancha, Campus Universitario s/n, 13071 Ciudad Real (Spain); Rodrigo, Manuel A., E-mail: manuel.rodrigo@uclm.es [Department of Chemical Engineering, Faculty of Chemical Sciences & Technologies, University of Castilla-La Mancha, Campus Universitario s/n, 13071 Ciudad Real (Spain); Sáez, Cristina; Cañizares, Pablo [Department of Chemical Engineering, Faculty of Chemical Sciences & Technologies, University of Castilla-La Mancha, Campus Universitario s/n, 13071 Ciudad Real (Spain)

    2016-09-05

    Highlights: • Moisture and compaction of soil must be re-establish in Scale-up of EKR. • Degree of compaction of soil depends on moisture, type of soil and EKR reactor. • Scale of EKR process determines the energy consumption in the treatment. • Electroosmosis and electromigration processes are favoured in prototype scale. • In real scale EKR processes it is important determine evaporation and leaks effects. - Abstract: This study analyses the effect of the scale-up of electrokinetic remediation (EKR) processes in natural soils. A procedure is proposed to prepare soils based on a compacting process to obtaining soils with similar moisture content and density to those found in real soils in the field. The soil used here was from a region with a high agrarian activity (Mora, Spain). The scale-up study was performed in two installations at different scales: a mock-up pilot scale (0.175 m{sup 3}) and a prototype with a scale that was very similar to a real application (16 m{sup 3}). The electrode configuration selected consisted of rows of graphite electrodes facing each other located in electrolyte wells. The discharge of 20 mg of 2,4-dichlorophenoxyacetic acid [2,4-D] per kg of dry soil was treated by applying an electric potential gradient of 1 V cm{sup −1}. An increase in scale was observed to directly influence the amount of energy supplied to the soil being treated. As a result, electroosmotic and electromigration flows and electric heating are more intense than in smaller-scale tests (24%, 1% and 25%, respectively respect to the values in prototype). In addition, possible leaks were evaluated by conducting a watertightness test and quantifying evaporation losses.

  7. Safety issues in scale-up of chemical processes.

    Science.gov (United States)

    Stoessel, F

    2001-11-01

    Fast time-to-market is an important issue in the development of chemical processes for fine chemicals and drug production. However, this needs to be balanced against the equally important issue of process safety. Developing a safe process within a short time frame is a demanding challenge but advances in: (i) risk analysis methods; (ii) procurement and interpretation of safety and scale-up data; and (iii) process control have opened up new perspectives in this field. The thermal stability of chemicals during storage and transportation is another field of interest, and data obtained from research in this area should allow the simplification of certain tedious procedures.

  8. The First Scale-Up Production of Theranostic Nanoemulsions

    Science.gov (United States)

    Liu, Lu; Bagia, Christina; Janjic, Jelena M.

    2015-01-01

    Abstract Theranostic nanomedicines are a promising new technological advancement toward personalized medicine. Although much progress has been made in pre-clinical studies, their clinical utilization is still under development. A key ingredient for successful theranostic clinical translation is pharmaceutical process design for production on a sufficient scale for clinical testing. In this study, we report, for the first time, a successful scale-up of a model theranostic nanoemulsion. Celecoxib-loaded near-infrared-labeled perfluorocarbon nanoemulsion was produced on three levels of scale (small at 54 mL, medium at 270 mL, and large at 1,000 mL) using microfluidization. The average size and polydispersity were not affected by the equipment used or production scale. The overall nanoemulsion stability was maintained for 90 days upon storage and was not impacted by nanoemulsion production scale or composition. Cell-based evaluations show comparable results for all nanoemulsions with no significant impact of nanoemulsion scale on cell toxicity and their pharmacological effects. This report serves as the first example of a successful scale-up of a theranostic nanoemulsion and a model for future studies on theranostic nanomedicine production and development. PMID:26309798

  9. Tissue strands as "bioink" for scale-up organ printing.

    Science.gov (United States)

    Yu, Yin; Ozbolat, Ibrahim T

    2014-01-01

    Organ printing, takes tissue spheroids as building blocks together with additive manufacturing technique to engineer tissue or organ replacement parts. Although a wide array of cell aggregation techniques has been investigated, and gained noticeable success, the application of tissue spheroids for scale-up tissue fabrication is still worth investigation. In this paper, we introduce a new micro-fabrication technique to create tissue strands at the scale of 500-700μm as a "bioink" for future robotic tissue printing. Printable alginate micro-conduits are used as semi-permeable capsules for tissue strand fabrication. Mouse insulinoma beta TC3 cell tissue strands were formed upon 4 days post fabrication with reasonable mechanical strength, high cell viability close to 90%, and tissue specific markers expression. Fusion was readily observed between strands when placing them together as early as 24h. Also, tissue strands were deposited with human umbilical vein smooth muscle cells (HUVSMCs) vascular conduits together to fabricated miniature pancreatic tissue analog. Our study provided a novel technique using tissue strands as "bioink" for scale-up bioprinting of tissues or organs.

  10. Quantification of ethanol methyl 1H magnetic resonance signal intensity following intravenous ethanol administration in primate brain

    OpenAIRE

    Flory, Graham S.; O’Malley, Jean; Grant, Kathleen A.; Park, Byung; Kroenke, Christopher D.

    2009-01-01

    In vivo 1H magnetic resonance spectroscopy (MRS) can be used to directly monitor brain ethanol. Previously, studies of human subjects have lead to the suggestion that the ethanol methyl 1H MRS signal intensity relates to tolerance to ethanol’s intoxicating effects. More recently, the ethanol 1H MRS signal intensity has been recognized to vary between brain gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) due to differences in T2 within these environments. The methods present...

  11. Autoradiographical detection of cholecystokinin-A receptors in primate brain using sup 125 I-Bolton Hunter CCK-8 and 3H-MK-329

    Energy Technology Data Exchange (ETDEWEB)

    Hill, D.R.; Shaw, T.M.; Graham, W.; Woodruff, G.N. (Merck Sharp and Dohme Research Laboratories, Harlow, Essex (England))

    1990-04-01

    In vitro autoradiography was performed in order to visualize cholecystokinin-A (CCK-A) receptors in sections of Cynomolgus monkey brain. CCK-A receptors were defined as those which displayed high affinity for the selective non-peptide antagonist MK-329 (L-364,718) and were detected in several regions by selective inhibition of 125I-Bolton Hunter CCK using MK-329 or direct labeling with 3H-MK-329. In the caudal medulla, high densities of CCK-A sites were present in the nucleus tractus solitarius, especially the caudal and medial aspects, and also the dorsal motor nucleus of the vagus. CCK-A sites were localized to a number of hypothalamic nuclei such as the supraoptic and paraventricular nuclei, the dorsomedial and infundibular nuclei as well as the neurohypophysis. The mammillary bodies and supramammillary nuclei also contained CCK-A receptor sites. High concentrations of CCK-A receptors were present in the substantia nigra zona compacta and also the ventral tegmental area and may be associated with dopamine cell bodies. Binding of 3H-MK-329 was also detected in parts of the caudate nucleus and ventral putamen. The detection, by autoradiographical means, of CCK-A receptors throughout the Cynomolgus monkey brain contrasts with similar studies performed using rodents and suggests differences in the density and, perhaps, the importance of CCK-A receptors in the primate as opposed to the rodent. The data suggest the possibility that CCK-A receptors may be involved in a number of important brain functions as diverse as the processing of sensory information from the gut, the regulation of hormone secretion, and the activity of dopamine cell activity.

  12. Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington's disease

    Directory of Open Access Journals (Sweden)

    Piotr Hadaczek

    2016-01-01

    Full Text Available Huntington's disease (HD is caused by a toxic gain-of-function associated with the expression of the mutant huntingtin (htt protein. Therefore, the use of RNA interference to inhibit Htt expression could represent a disease-modifying therapy. The potential of two recombinant adeno-associated viral vectors (AAV, AAV1 and AAV2, to transduce the cortico-striatal tissues that are predominantly affected in HD was explored. Green fluorescent protein was used as a reporter in each vector to show that both serotypes were broadly distributed in medium spiny neurons in the striatum and cortico-striatal neurons after infusion into the putamen and caudate nucleus of nonhuman primates (NHP, with AAV1-directed expression being slightly more robust than AAV2-driven expression. This study suggests that both serotypes are capable of targeting neurons that degenerate in HD, and it sets the stage for the advanced preclinical evaluation of an RNAi-based therapy for this disease.

  13. Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington’s disease

    Science.gov (United States)

    Hadaczek, Piotr; Stanek, Lisa; Ciesielska, Agnieszka; Sudhakar, Vivek; Samaranch, Lluis; Pivirotto, Philip; Bringas, John; O’Riordan, Catherine; Mastis, Bryan; San Sebastian, Waldy; Forsayeth, John; Cheng, Seng H; Bankiewicz, Krystof S; Shihabuddin, Lamya S

    2016-01-01

    Huntington’s disease (HD) is caused by a toxic gain-of-function associated with the expression of the mutant huntingtin (htt) protein. Therefore, the use of RNA interference to inhibit Htt expression could represent a disease-modifying therapy. The potential of two recombinant adeno-associated viral vectors (AAV), AAV1 and AAV2, to transduce the cortico-striatal tissues that are predominantly affected in HD was explored. Green fluorescent protein was used as a reporter in each vector to show that both serotypes were broadly distributed in medium spiny neurons in the striatum and cortico-striatal neurons after infusion into the putamen and caudate nucleus of nonhuman primates (NHP), with AAV1-directed expression being slightly more robust than AAV2-driven expression. This study suggests that both serotypes are capable of targeting neurons that degenerate in HD, and it sets the stage for the advanced preclinical evaluation of an RNAi-based therapy for this disease. PMID:27408903

  14. TA Beliefs in a SCALE-UP Style Classroom

    Science.gov (United States)

    DeBeck, George; Settelmeyer, Sam; Li, Sissi; Demaree, Dedra

    2010-10-01

    In Spring 2010, the Oregon State University physics department instituted a SCALE-UP (Student-Centered Active Learning Environment for Undergraduate Programs) style studio classroom in the introductory, calculus-based physics series. In our initial implementation, comprised of two hours lecture, two hours of studio, and two hours lab work, the studio session was lead by a faculty member and either 2 GTAs or 1 GTA and 1 LA. We plan to move to a model where senior GTAs can lead studio sections after co-teaching with the faculty member. It is critical that we know how to prepare and support the instructional team in facilitating student learning in this setting. We examine GTA and LA pedagogical beliefs through reflective journaling, interviews, and personal experience of the authors. In particular, we examine how these beliefs changed over their first quarter of instruction, as well as the resources used to adapt to the new classroom environment.

  15. Scale-Up of GRCop: From Laboratory to Rocket Engines

    Science.gov (United States)

    Ellis, David L.

    2016-01-01

    GRCop is a high temperature, high thermal conductivity copper-based series of alloys designed primarily for use in regeneratively cooled rocket engine liners. It began with laboratory-level production of a few grams of ribbon produced by chill block melt spinning and has grown to commercial-scale production of large-scale rocket engine liners. Along the way, a variety of methods of consolidating and working the alloy were examined, a database of properties was developed and a variety of commercial and government applications were considered. This talk will briefly address the basic material properties used for selection of compositions to scale up, the methods used to go from simple ribbon to rocket engines, the need to develop a suitable database, and the issues related to getting the alloy into a rocket engine or other application.

  16. Scaling Up Family Therapy in Fragile, Conflict-Affected States.

    Science.gov (United States)

    Charlés, Laurie L

    2015-09-01

    This article discusses the design and delivery of two international family therapy-focused mental health and psychosocial support training projects, one in a fragile state and one in a post-conflict state. The training projects took place in Southeast Asia and the Middle East/North Africa. Each was funded, supported, and implemented by local, regional, and international stakeholders, and delivered as part of a broader humanitarian agenda to develop human resource capacity to work with families affected by atrocities. The two examples illustrate how task-shifting/task-sharing and transitional justice approaches were used to inform the scaling-up of professionals involved in each project. They also exemplify how state-citizen phenomena in each location affected the project design and delivery. © 2014 Family Process Institute.

  17. Development and application of a modified dynamic time warping algorithm (DTW-S to analyses of primate brain expression time series

    Directory of Open Access Journals (Sweden)

    Vingron Martin

    2011-08-01

    Full Text Available Abstract Background Comparing biological time series data across different conditions, or different specimens, is a common but still challenging task. Algorithms aligning two time series represent a valuable tool for such comparisons. While many powerful computation tools for time series alignment have been developed, they do not provide significance estimates for time shift measurements. Results Here, we present an extended version of the original DTW algorithm that allows us to determine the significance of time shift estimates in time series alignments, the DTW-Significance (DTW-S algorithm. The DTW-S combines important properties of the original algorithm and other published time series alignment tools: DTW-S calculates the optimal alignment for each time point of each gene, it uses interpolated time points for time shift estimation, and it does not require alignment of the time-series end points. As a new feature, we implement a simulation procedure based on parameters estimated from real time series data, on a series-by-series basis, allowing us to determine the false positive rate (FPR and the significance of the estimated time shift values. We assess the performance of our method using simulation data and real expression time series from two published primate brain expression datasets. Our results show that this method can provide accurate and robust time shift estimates for each time point on a gene-by-gene basis. Using these estimates, we are able to uncover novel features of the biological processes underlying human brain development and maturation. Conclusions The DTW-S provides a convenient tool for calculating accurate and robust time shift estimates at each time point for each gene, based on time series data. The estimates can be used to uncover novel biological features of the system being studied. The DTW-S is freely available as an R package TimeShift at http://www.picb.ac.cn/Comparative/data.html.

  18. Amphetamine decreases α2C-adrenoceptor binding of [11C]ORM-13070: a PET study in the primate brain.

    Science.gov (United States)

    Finnema, Sjoerd J; Hughes, Zoë A; Haaparanta-Solin, Merja; Stepanov, Vladimir; Nakao, Ryuji; Varnäs, Katarina; Varrone, Andrea; Arponen, Eveliina; Marjamäki, Päivi; Pohjanoksa, Katariina; Vuorilehto, Lauri; Babalola, Phebian A; Solin, Olof; Grimwood, Sarah; Sallinen, Jukka; Farde, Lars; Scheinin, Mika; Halldin, Christer

    2014-12-13

    The neurotransmitter norepinephrine has been implicated in psychiatric and neurodegenerative disorders. Examination of synaptic norepinephrine concentrations in the living brain may be possible with positron emission tomography (PET), but has been hampered by the lack of suitable radioligands. We explored the use of the novel α2C-adrenoceptor antagonist PET tracer [(11)C]ORM-13070 for measurement of amphetamine-induced changes in synaptic norepinephrine. The effect of amphetamine on [(11)C]ORM-13070 binding was evaluated ex vivo in rat brain sections and in vivo with PET imaging in monkeys. Microdialysis experiments confirmed amphetamine-induced elevations in rat striatal norepinephrine and dopamine concentrations. Regional [(11)C]ORM-13070 receptor binding was high in the striatum and low in the cerebellum. After injection of [(11)C]ORM-13070 in rats, mean striatal specific binding ratios, determined using cerebellum as a reference region, were 1.4±0.3 after vehicle pretreatment and 1.2±0.2 after amphetamine administration (0.3mg/kg, subcutaneous). Injection of [(11)C]ORM-13070 in non-human primates resulted in mean striatal binding potential (BP ND) estimates of 0.65±0.12 at baseline. Intravenous administration of amphetamine (0.5 and 1.0mg/kg, i.v.) reduced BP ND values by 31-50%. Amphetamine (0.3mg/kg, subcutaneous) increased extracellular norepinephrine (by 400%) and dopamine (by 270%) in rat striata. Together, these results indicate that [(11)C]ORM-13070 may be a useful tool for evaluation of synaptic norepinephrine concentrations in vivo. Future studies are required to further understand a potential contribution of dopamine to the amphetamine-induced effect. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  19. Transduction of nonhuman primate brain with adeno-associated virus serotype 1: vector trafficking and immune response.

    Science.gov (United States)

    Hadaczek, Piotr; Forsayeth, John; Mirek, Hanna; Munson, Keith; Bringas, John; Pivirotto, Phil; McBride, Jodi L; Davidson, Beverly L; Bankiewicz, Krystof S

    2009-03-01

    We used convection-enhanced delivery (CED) to characterize gene delivery mediated by adeno-associated virus type 1 (AAV1) by tracking expression of hrGFP (humanized green fluorescent protein from Renilla reniformis) into the striatum, basal forebrain, and corona radiata of monkey brain. Four cynomolgus monkeys received single infusions into corona radiata, putamen, and caudate. The other group (n = 4) received infusions into basal forebrain. Thirty days after infusion animals were killed and their brains were processed for immunohistochemical evaluation. Volumetric analysis of GFP-positive brain areas was performed. AAV1-hrGFP infusions resulted in approximately 550, 700, and 73 mm(3) coverage after infusion into corona radiata, striatum, and basal forebrain, respectively. Aside from targeted regions, other brain structures also showed GFP signal (internal and external globus pallidus, subthalamic nucleus), supporting the idea that AAV1 is actively trafficked to regions distal from the infusion site. In addition to neuronal transduction, a significant nonneuronal cell population was transduced by AAV1 vector; for example, oligodendrocytes in corona radiata and astrocytes in the striatum. We observed a strong humoral and cell-mediated response against AAV1-hrGFP in transduced monkeys irrespective of the anatomic location of the infusion, as evidenced by induction of circulating anti-AAV1 and anti-hrGFP antibodies, as well as infiltration of CD4(+) lymphocytes and upregulation of MHC-II in regions infused with vector. We conclude that transduction of antigen-presenting cells within the CNS is a likely cause of this response and that caution is warranted when foreign transgenes are used as reporters in gene therapy studies with vectors with broader tropism than AAV2.

  20. Challenges and Opportunities in Scaling-Up Nutrition in Healthcare

    Directory of Open Access Journals (Sweden)

    Ian Darnton-Hill

    2015-01-01

    Full Text Available Healthcare continues to be in a state of flux; conventionally, this provides opportunities and challenges. The opportunities include technological breakthroughs, improved economies and increasing availability of healthcare. On the other hand, economic disparities are increasing and leading to differing accessibility to healthcare, including within affluent countries. Nutrition has received an increase in attention and resources in recent decades, a lot of it stimulated by the rise in obesity, type 2 diabetes mellitus and hypertension. An increase in ageing populations also has meant increased interest in nutrition-related chronic diseases. In many middle-income countries, there has been an increase in the double burden of malnutrition with undernourished children and overweight/obese parents and adolescents. In low-income countries, an increased evidence base has allowed scaling-up of interventions to address under-nutrition, both nutrition-specific and nutrition-sensitive interventions. Immediate barriers (institutional, structural and biological and longer-term barriers (staffing shortages where most needed and environmental impacts on health are discussed. Significant barriers remain for the near universal access to healthcare, especially for those who are socio-economically disadvantaged, geographically isolated, living in war zones or where environmental damage has taken place. However, these barriers are increasingly being recognized, and efforts are being made to address them. The paper aims to take a broad view that identifies and then comments on the many social, political and scientific factors affecting the achievement of improved nutrition through healthcare.

  1. Scale-up activation of carbon fibres for hydrogen storage

    Energy Technology Data Exchange (ETDEWEB)

    Kunowsky, M.; Marco-Lozar, J.P.; Cazorla-Amoros, D.; Linares-Solano, A. [Grupo de Materiales Carbonosos y Medio Ambiente, Departamento de Quimica Inorganica, Universidad de Alicante, Ap. 99, E-03080 Alicante (Spain)

    2010-03-15

    In a previous study, we investigated, at a laboratory scale, the chemical activation of two different carbon fibres (CF), their porosity characterization, and their optimization for hydrogen storage. In the present work, this study is extended to: (i) a larger range of KOH activated carbon fibres, (ii) a larger range of hydrogen adsorption measurements at different temperatures and pressures (i.e. at room temperature, up to 20 MPa, and at 77 K, up to 4 MPa), and (iii) a scaling-up activation approach in which the obtained activated carbon fibres (ACF) are compared with those from laboratory-scale activation. The prepared samples cover a large range of porosities, which is found to govern their ability for hydrogen adsorption. The hydrogen uptake capacities of all the prepared samples have been analysed both in volumetric and in gravimetric bases. Thus, maximum adsorption capacities of around 5 wt% are obtained at 77 K, and 1.1 wt% at room temperature, respectively. The packing densities of the materials have been measured, turning out to play an important role in order to estimate the total storage capacity of a tank volume. Maximum values of 17.4 g l{sup -1} at 298 K, and 38.6 g l{sup -1} at 77 K were obtained. (author)

  2. Effective scale-up: avoiding the same old traps

    Directory of Open Access Journals (Sweden)

    Nelson David

    2009-01-01

    Full Text Available Abstract Despite progress in developing more effective training methodologies, training initiatives for health workers continue to experience common pitfalls that have beset the overall success and cost-effectiveness of these programs for decades. These include lack of country-level coordination of health training, inequitable access to training, interrupted services, and failure to reinforce skills and knowledge training by addressing other performance factors. These pitfalls are now seen as aggravating the current crisis in human resources for health and impeding the effective scale-up of training and the potential impact of promising strategies such as task shifting to address health worker shortages. Drawing on IntraHealth International's lessons learned in designing reproductive health and HIV/AIDS training and performance improvement programmes, this commentary discusses promising practices for strengthening human resources for health through more efficient and effective training and learning programmes that avoid the same old traps. These promising practices include the following: Assessing performance gaps and opportunities before designing a training initiative; addressing performance factors other than skills and knowledge that health workers need to perform well; applying a "learning for performance" approach; standardizing curricula throughout a country; linking pre-service education, in-service training and professional associations; enhancing traditional education; strengthening human resources information systems to improve workforce planning, policies and management; applying technology to meet training needs.

  3. Scale-up of a new bacterial mannitol production process.

    Science.gov (United States)

    von Weymarn, F Niklas W; Kiviharju, Kristiina J; Jääskeläinen, Seppo T; Leisola, Matti S A

    2003-01-01

    D-Mannitol is a sugar alcohol with applications in chemistry, food and pharmaceutical industries, and medicine. Commercially, mannitol is produced by catalytic hydrogenation. Although this process is widely used, it is not optimal for mannitol production. New processes, including chemical, enzymatic, and microbial processes, are frequently developed and evaluated against the existing hydrogenation processes. In earlier papers, we have described the identification of a food-grade lactic acid bacterium strain, Leuconostoc mesenteroides ATCC-9135, with efficient mannitol production capabilities and the development and optimization of a new bioprocess in which the strain was applied. The new bioprocess is simple. It requires a reduced bioreactor with the following features: sterilization, pH and T control (at mild conditions), and slow mixing. The contamination risk of the new bioprocess is low, and the downstream processing protocol comprises simple, widely used unit operations: evaporation, crystallization, crystal separation, and drying. On a 2-L laboratory scale, high mannitol yields from fructose (93-97%) and volumetric mannitol productivities (>20 g L(-1) h(-1)) were achieved. In this paper, the scalability of the new bioprocess was tested on a small pilot scale (100 L). In the pilot plant, production levels were achieved similar to those in the laboratory. Also, high-purity mannitol crystals were obtained at similar yield levels. The results presented in this paper indicate that the new bioprocess can easily be scaled-up to an industrial scale and that the production levels achieved with it are comparable to the catalytic hydrogenation processes.

  4. Fungal biosynthesis of gold nanoparticles: mechanism and scale up.

    Science.gov (United States)

    Kitching, Michael; Ramani, Meghana; Marsili, Enrico

    2015-11-01

    Gold nanoparticles (AuNPs) are a widespread research tool because of their oxidation resistance, biocompatibility and stability. Chemical methods for AuNP synthesis often produce toxic residues that raise environmental concern. On the other hand, the biological synthesis of AuNPs in viable microorganisms and their cell-free extracts is an environmentally friendly and low-cost process. In general, fungi tolerate higher metal concentrations than bacteria and secrete abundant extracellular redox proteins to reduce soluble metal ions to their insoluble form and eventually to nanocrystals. Fungi harbour untapped biological diversity and may provide novel metal reductases for metal detoxification and bioreduction. A thorough understanding of the biosynthetic mechanism of AuNPs in fungi is needed to reduce the time of biosynthesis and to scale up the AuNP production process. In this review, we describe the known mechanisms for AuNP biosynthesis in viable fungi and fungal protein extracts and discuss the most suitable bioreactors for industrial AuNP biosynthesis. © 2014 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  5. Fungal biosynthesis of gold nanoparticles: mechanism and scale up

    Science.gov (United States)

    Kitching, Michael; Ramani, Meghana; Marsili, Enrico

    2015-01-01

    Gold nanoparticles (AuNPs) are a widespread research tool because of their oxidation resistance, biocompatibility and stability. Chemical methods for AuNP synthesis often produce toxic residues that raise environmental concern. On the other hand, the biological synthesis of AuNPs in viable microorganisms and their cell-free extracts is an environmentally friendly and low-cost process. In general, fungi tolerate higher metal concentrations than bacteria and secrete abundant extracellular redox proteins to reduce soluble metal ions to their insoluble form and eventually to nanocrystals. Fungi harbour untapped biological diversity and may provide novel metal reductases for metal detoxification and bioreduction. A thorough understanding of the biosynthetic mechanism of AuNPs in fungi is needed to reduce the time of biosynthesis and to scale up the AuNP production process. In this review, we describe the known mechanisms for AuNP biosynthesis in viable fungi and fungal protein extracts and discuss the most suitable bioreactors for industrial AuNP biosynthesis. PMID:25154648

  6. Polyethylene encapsulation of mixed wastes: Scale-up feasibility

    Energy Technology Data Exchange (ETDEWEB)

    Kalb, P.D.; Heiser, J.H.; Colombo, P.

    1991-12-31

    A polyethylene process for the improved encapsulation of radioactive, hazardous, and mixed wastes have been developed at Brookhaven National Laboratory (BNL). Improvements in waste loading and waste form performance have been demonstrated through bench-scale development and testing. Maximum waste loadings of up to 70 dry wt % mixed waste nitrate salt were achieved, compared with 13--20 dry wt % using conventional cement processes. Stability under anticipated storage and disposal conditions and compliance with applicable hazardous waste regulations were demonstrated through a series of lab-scale waste form performance tests. Full-scale demonstration of this process using actual or surrogate waste is currently planned. A scale-up feasibility test was successfully conducted, demonstrating the ability to process nitrate salts at production rates (up to 450 kg/hr) and the close agreement between bench- and full-scale process parameters. Cored samples from the resulting pilot-scale (114 liter) waste form were used to verify homogeneity and to provide additional specimens for confirmatory performance testing.

  7. Scaling Up Data-Centric Middleware on a Cluster Computer

    Energy Technology Data Exchange (ETDEWEB)

    Liu, D T; Franklin, M J; Garlick, J; Abdulla, G M

    2005-04-29

    Data-centric workflow middleware systems are workflow systems that treat data as first class objects alongside programs. These systems improve the usability, responsiveness and efficiency of workflow execution over cluster (and grid) computers. In this work, we explore the scalability of one such system, GridDB, on cluster computers. We measure the performance and scalability of GridDB in executing data-intensive image processing workflows from the SuperMACHO astrophysics survey on a large cluster computer. Our first experimental study concerns the scale-up of GridDB. We make a rather surprising finding, that while the middleware system issues many queries and transactions to a DBMS, file system operations present the first-tier bottleneck. We circumvent this bottleneck and increase the scalability of GridDB by more than 2-fold on our image processing application (up to 128 nodes). In a second study, we demonstrate the sensitivity of GridDB performance (and therefore application performance) to characteristics of the workflows being executed. To manage these sensitivities, we provide guidelines for trading off the costs and benefits of GridDB at a fine-grain.

  8. The evolution of neocortex in primates.

    Science.gov (United States)

    Kaas, Jon H

    2012-01-01

    We can learn about the evolution of neocortex in primates through comparative studies of cortical organization in primates and those mammals that are the closest living relatives of primates, in conjunction with brain features revealed by the skull endocasts of fossil archaic primates. Such studies suggest that early primates had acquired a number of features of neocortex that now distinguish modern primates. Most notably, early primates had an array of new visual areas, and those visual areas widely shared with other mammals had been modified. Posterior parietal cortex was greatly expanded with sensorimotor modules for reaching, grasping, and personal defense. Motor cortex had become more specialized for hand use, and the functions of primary motor cortex were enhanced by the addition and development of premotor and cingulate motor areas. Cortical architecture became more varied, and cortical neuron populations became denser overall than in nonprimate ancestors. Primary visual cortex had the densest population of neurons, and this became more pronounced in the anthropoid radiation. Within the primate clade, considerable variability in cortical size, numbers of areas, and architecture evolved. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Scaling-up ultrasound standing wave enhanced sedimentation filters.

    Science.gov (United States)

    Prest, Jeff E; Treves Brown, Bernard J; Fielden, Peter R; Wilkinson, Stephen J; Hawkes, Jeremy J

    2015-02-01

    Particle concentration and filtration is a key stage in a wide range of processing industries and also one that can be present challenges for high throughput, continuous operation. Here we demonstrate some features which increase the efficiency of ultrasound enhanced sedimentation and could enable the technology the potential to be scaled up. In this work, 20 mm piezoelectric plates were used to drive 100 mm high chambers formed from single structural elements. The coherent structural resonances were able to drive particles (yeast cells) in the water to nodes throughout the chamber. Ultrasound enhanced sedimentation was used to demonstrate the efficiency of the system (>99% particle clearance). Sub-wavelength pin protrusions were used for the contacts between the resonant chamber and other elements. The pins provided support and transferred power, replacing glue which is inefficient for power transfer. Filtration energies of ∼4 J/ml of suspension were measured. A calculation of thermal convection indicates that the circulation could disrupt cell alignment in ducts >35 mm high when a 1K temperature gradient is present; we predict higher efficiencies when this maximum height is observed. For the acoustic design, although modelling was minimal before construction, the very simple construction allowed us to form 3D models of the nodal patterns in the fluid and the duct structure. The models were compared with visual observations of particle movement, Chladni figures and scanning laser vibrometer mapping. This demonstrates that nodal planes in the fluid can be controlled by the position of clamping points and that the contacts could be positioned to increase the efficiency and reliability of particle manipulations in standing waves. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Medical Specialties in Oman: Scaling Up through National Action.

    Science.gov (United States)

    Alshishtawy, Moeness

    2009-10-01

    To analyze the situation of medical specialists in the Sultanate of Oman, in terms of its past and current size and future needs. Data of Oman Medical Specialty Board (OMSB) and Ministry of Health (MoH) on medical specialists in Oman and the current Omanization levels in various specialties were reviewed and analyzed. Projections of the need for medical specialists by the End-2020 and in 2032 were calculated based on three different scenarios. Data on the number of medical specialists in Oman revealed a steady increase over the years, starting from only 52 specialists in 1975 to 2,162 in 2008; 25.1% of them were Omanis. The ratios of Omanization showed some inconsistency over the years in certain categories of specialization and were considerably low in some important specialties, e.g. Anesthesiology (5.7%) and Obstetrics & Gynecology (18.5%). By the End-2020, the total workforce of medical specialists in Oman is expected to reach 2,228; 408 of them would be Omanis. Otherwise, to achieve 100% Omanization, the number of Omani specialists required would be 1,772. According to three different scenarios, the number of medical specialists in Oman would range from 2,785-4,569 by 2032; of them 1,859-3,646 would be Omanis. In order to rapidly increase the number of medical specialists in Oman to satisfy the country's needs, OMSB has to adopt a visionary long-term strategy, through which it wouldß be able to gather all stakeholders resources within a national framework and direct a significant investment of funds towards scaling up medical specialists production.

  11. Scaling up debris-flow experiments on a centrifuge

    Science.gov (United States)

    Hung, C.; Capart, H.; Crone, T. J.; Grinspum, E.; Hsu, L.; Kaufman, D.; Li, L.; Ling, H.; Reitz, M. D.; Smith, B.; Stark, C. P.

    2013-12-01

    Boundary forces generated by debris flows can be powerful enough to erode bedrock and cause considerable damage to infrastructure during runout. Formulation of an erosion-rate law for debris flows is therefore a high priority, and it makes sense to build such a law around laboratory experiments. However, running experiments big enough to generate realistic boundary forces is a logistical challenge to say the least [1]. One alternative is to run table-top simulations with unnaturally weak but fast-eroding pseudo-bedrock, another is to extrapolate from micro-erosion of natural substrates driven by unnaturally weak impacts; hybrid-scale experiments have also been conducted [2]. Here we take a different approach in which we scale up granular impact forces by running our experiments under enhanced gravity in a geotechnical centrifuge [3]. Using a 40cm-diameter rotating drum [2] spun at up to 100g, we generate debris flows with an effective depth of over several meters. By varying effective gravity from 1g to 100g we explore the scaling of granular flow forces and the consequent bed and wall erosion rates. The velocity and density structure of these granular flows is monitored using laser sheets, high-speed video, and particle tracking [4], and the progressive erosion of the boundary surfaces is measured by laser scanning. The force structures and their fluctuations within the granular mass and at the boundaries are explored with contact dynamics numerical simulations that mimic the lab experimental conditions [5]. In this presentation we summarize these results and discuss how they can contribute to the formulation of debris-flow erosion law. [1] Major, J. J. (1997), Journal of Geology 105: 345-366, doi:10.1086/515930 [2] Hsu, L. (2010), Ph.D. thesis, University of California, Berkeley [3] Brucks, A., et al (2007), Physical Review E 75, 032301, doi:10.1103/PhysRevE.75.032301 [4] Spinewine, B., et al (2011), Experiments in Fluids 50: 1507-1525, doi: 10.1007/s00348

  12. Fenfluramine Reduces [11C]Cimbi-36 Binding to the 5-HT2A Receptor in the Nonhuman Primate Brain

    DEFF Research Database (Denmark)

    Yang, Kai-Chun; Stepanov, Vladimir; Martinsson, Stefan

    2017-01-01

    Background: [11C]Cimbi-36 is a serotonin 2A receptor agonist positron emission tomography radioligand that has recently been examined in humans. The binding of agonist radioligand is expected to be more sensitive to endogenous neurotransmitter concentrations than antagonist radioligands. In the c......Background: [11C]Cimbi-36 is a serotonin 2A receptor agonist positron emission tomography radioligand that has recently been examined in humans. The binding of agonist radioligand is expected to be more sensitive to endogenous neurotransmitter concentrations than antagonist radioligands....... In the current study, we compared the effect of serotonin releaser fenfluramine on the binding of [11C]Cimbi-36, [11C]MDL 100907 (a serotonin 2A receptor antagonist radioligand), and [11C]AZ10419369 (a serotonin 1B receptor partial agonist radioligand with established serotonin sensitivity) in the monkey brain...... binding potential were larger than for [11C]AZ10419369 in neocortical and limbic regions (~35%) but smaller in striatum and thalamus (~40%). Decreases in [11C]Cimbi-36 binding potential were 0.9 to 2.8 times larger than for [11C]MDL 100907, and the fraction of serotonin 2A receptor in the high...

  13. Primate photopigments and primate color vision.

    OpenAIRE

    Jacobs, G H

    1996-01-01

    The past 15 years have brought much progress in our understanding of several basic features of primate color vision. There has been particular success in cataloging the spectral properties of the cone photopigments found in retinas of a number of primate species and in elucidating the relationship between cone opsin genes and their photopigment products. Direct studies of color vision show that there are several modal patterns of color vision among groupings of primates: (i) Old World monkeys...

  14. Subject-specific modulation of local field potential spectral power during brain-machine interface control in primates

    Science.gov (United States)

    So, Kelvin; Dangi, Siddharth; Orsborn, Amy L.; Gastpar, Michael C.; Carmena, Jose M.

    2014-04-01

    Objective. Intracortical brain-machine interfaces (BMIs) have predominantly utilized spike activity as the control signal. However, an increasing number of studies have shown the utility of local field potentials (LFPs) for decoding motor related signals. Currently, it is unclear how well different LFP frequencies can serve as features for continuous, closed-loop BMI control. Approach. We demonstrate 2D continuous LFP-based BMI control using closed-loop decoder adaptation, which adapts decoder parameters to subject-specific LFP feature modulations during BMI control. We trained two macaque monkeys to control a 2D cursor in a center-out task by modulating LFP power in the 0-150 Hz range. Main results. While both monkeys attained control, they used different strategies involving different frequency bands. One monkey primarily utilized the low-frequency spectrum (0-80 Hz), which was highly correlated between channels, and obtained proficient performance even with a single channel. In contrast, the other monkey relied more on higher frequencies (80-150 Hz), which were less correlated between channels, and had greater difficulty with control as the number of channels decreased. We then restricted the monkeys to use only various sub-ranges (0-40, 40-80, and 80-150 Hz) of the 0-150 Hz band. Interestingly, although both monkeys performed better with some sub-ranges than others, they were able to achieve BMI control with all sub-ranges after decoder adaptation, demonstrating broad flexibility in the frequencies that could potentially be used for LFP-based BMI control. Significance. Overall, our results demonstrate proficient, continuous BMI control using LFPs and provide insight into the subject-specific spectral patterns of LFP activity modulated during control.

  15. Characterization of [{sup 11}C]Lu AE92686 as a PET radioligand for phosphodiesterase 10A in the nonhuman primate brain

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Kai-Chun; Stepanov, Vladimir; Amini, Nahid; Martinsson, Stefan; Takano, Akihiro; Halldin, Christer [Karolinska Institutet, Karolinska University Hospital, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm (Sweden); Nielsen, Jacob [H. Lundbeck A/S, Synaptic Transmission, Valby (Denmark); Bundgaard, Christoffer; Bang-Andersen, Benny [H. Lundbeck A/S, Discovery Chemistry and DMPK, Valby (Denmark); Grimwood, Sarah [Pfizer Inc., Neuroscience and Pain Research Unit, Cambridge, MA (United States); Farde, Lars [Karolinska Institutet, Karolinska University Hospital, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm (Sweden); AstraZeneca PET Science Center at Karolinska Institutet, Personalized Health Care and Biomarkers, Stockholm (Sweden); Finnema, Sjoerd J. [Karolinska Institutet, Karolinska University Hospital, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm (Sweden); Yale University, Department of Radiology and Biomedical Imaging, New Haven, CT (United States)

    2017-02-15

    [{sup 11}C]Lu AE92686 is a positron emission tomography (PET) radioligand that has recently been validated for examining phosphodiesterase 10A (PDE10A) in the human striatum. [{sup 11}C]Lu AE92686 has high affinity for PDE10A (IC{sub 50} = 0.39 nM) and may also be suitable for examination of the substantia nigra, a region with low density of PDE10A. Here, we report characterization of regional [{sup 11}C]Lu AE92686 binding to PDE10A in the nonhuman primate (NHP) brain. A total of 11 PET measurements, seven baseline and four following pretreatment with unlabeled Lu AE92686 or the structurally unrelated PDE10A inhibitor MP-10, were performed in five NHPs using a high resolution research tomograph (HRRT). [{sup 11}C]Lu AE92686 binding was quantified using a radiometabolite-corrected arterial input function and compartmental and graphical modeling approaches. Regional time-activity curves were best described with the two-tissue compartment model (2TCM). However, the distribution volume (V{sub T}) values for all regions were obtained by the Logan plot analysis, as reliable cerebellar V{sub T} values could not be derived by the 2TCM. For cerebellum, a proposed reference region, V{sub T} values increased by ∝30 % with increasing PET measurement duration from 63 to 123 min, while V{sub T} values in target regions remained stable. Both pretreatment drugs significantly decreased [{sup 11}C]Lu AE92686 binding in target regions, while no significant effect on cerebellum was observed. Binding potential (BP{sub ND}) values, derived with the simplified reference tissue model (SRTM), were 13-17 in putamen and 3-5 in substantia nigra and correlated well to values from the Logan plot analysis. The method proposed for quantification of [{sup 11}C]Lu AE92686 binding in applied studies in NHP is based on 63 min PET data and SRTM with cerebellum as a reference region. The study supports that [{sup 11}C]Lu AE92686 can be used for PET examinations of PDE10A binding also in substantia

  16. Awake nonhuman primate brain PET imaging with minimal head restraint: evaluation of GABAA-benzodiazepine binding with 11C-flumazenil in awake and anesthetized animals.

    Science.gov (United States)

    Sandiego, Christine M; Jin, Xiao; Mulnix, Tim; Fowles, Krista; Labaree, David; Ropchan, Jim; Huang, Yiyun; Cosgrove, Kelly; Castner, Stacy A; Williams, Graham V; Wells, Lisa; Rabiner, Eugenii A; Carson, Richard E

    2013-11-01

    Neuroreceptor imaging in the nonhuman primate (NHP) is valuable for translational research approaches in humans. However, most NHP studies are conducted under anesthesia, which affects the interpretability of receptor binding measures. The aims of this study were to develop awake NHP imaging with minimal head restraint and to compare in vivo binding of the γ-aminobutyric acid type A (GABAA)-benzodiazepine radiotracer (11)C-flumazenil under anesthetized and awake conditions. We hypothesized that (11)C-flumazenil binding potential (BPND) would be higher in isoflurane-anesthetized monkeys. The small animal PET scanner was fitted to a mechanical device that raised and tilted the scanner 45° while the awake NHP was tilted back 35° in a custom chair for optimal brain positioning, which required acclimation of the animals to the chair, touch-screen tasks, intravenous catheter insertion, and tilting. For PET studies, the bolus-plus-constant infusion method was used for (11)C-flumazenil administration. Two rhesus monkeys were scanned under the awake (n = 6 scans) and isoflurane-anesthetized (n = 4 scans) conditions. An infrared camera was used to track head motion during PET scans. Under the awake condition, emission and head motion-tracking data were acquired for 40-75 min after injection. Anesthetized monkeys were scanned for 90 min. Cortisol measurements were acquired during awake and anesthetized scans. Equilibrium analysis was used for both the anesthetized (n = 4) and the awake (n = 5) datasets to compute mean BPND images in NHP template space, using the pons as a reference region. The percentage change per minute in radioactivity concentration was calculated in high- and low-binding regions to assess the quality of equilibrium. The monkeys acclimated to procedures in the NHP chair necessary to perform awake PET imaging. Image quality was comparable between awake and anesthetized conditions. The relationship between awake and anesthetized values was BPND (awake

  17. Adaptations to vision-for-action in primate brain evolution: Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib

    Science.gov (United States)

    Hecht, Erin

    2016-03-01

    As Arbib [1] notes, the two-streams hypothesis [5] has provided a powerful explanatory framework for understanding visual processing. The inferotemporal ventral stream recognizes objects and agents - ;what; one is seeing. The dorsal ;how; or ;where; stream through parietal cortex processes motion, spatial location, and visuo-proprioceptive relationships - ;vision for action.; Hickock and Poeppel's [3] extension of this model to the auditory system raises the question of deeper, multi- or supra-sensory themes in dorsal vs. ventral processing. Petrides and Pandya [10] postulate that the evolution of language may have been influenced by the fact that the dorsal stream terminates in posterior Broca's area (BA44) while the ventral stream terminates in anterior Broca's area (BA45). In an intriguing potential parallel, a recent ALE metanalysis of 54 fMRI studies found that semantic processing is located more anteriorly and superiorly than syntactic processing in Broca's area [13]. But clearly, macaques do not have language, nor other likely pre- or co-adaptations to language, such as complex imitation and tool use. What changed in the brain that enabled these functions to evolve?

  18. Why primate models matter.

    Science.gov (United States)

    Phillips, Kimberley A; Bales, Karen L; Capitanio, John P; Conley, Alan; Czoty, Paul W; 't Hart, Bert A; Hopkins, William D; Hu, Shiu-Lok; Miller, Lisa A; Nader, Michael A; Nathanielsz, Peter W; Rogers, Jeffrey; Shively, Carol A; Voytko, Mary Lou

    2014-09-01

    Research involving nonhuman primates (NHPs) has played a vital role in many of the medical and scientific advances of the past century. NHPs are used because of their similarity to humans in physiology, neuroanatomy, reproduction, development, cognition, and social complexity-yet it is these very similarities that make the use of NHPs in biomedical research a considered decision. As primate researchers, we feel an obligation and responsibility to present the facts concerning why primates are used in various areas of biomedical research. Recent decisions in the United States, including the phasing out of chimpanzees in research by the National Institutes of Health and the pending closure of the New England Primate Research Center, illustrate to us the critical importance of conveying why continued research with primates is needed. Here, we review key areas in biomedicine where primate models have been, and continue to be, essential for advancing fundamental knowledge in biomedical and biological research. © 2014 Wiley Periodicals, Inc.

  19. A model-based framework for incremental scale-up of wastewater treatment processes

    DEFF Research Database (Denmark)

    Mauricio Iglesias, Miguel; Sin, Gürkan

    Scale-up is traditionally done following specific ratios or rules of thumb which do not lead to optimal results. We present a generic framework to assist in scale-up of wastewater treatment processes based on multiscale modelling, multiobjective optimisation and a validation of the model at the new...

  20. 77 FR 25469 - Applications for New Awards; Investing in Innovation Fund, Scale-Up Grants

    Science.gov (United States)

    2012-04-30

    ... Applications for New Awards; Investing in Innovation Fund, Scale- Up Grants Catalog of Federal Domestic Assistance (CFDA) Number: 84.411A (Scale-up grants). AGENCY: Office of Innovation and Improvement, Department..., the Office of Innovation and Improvement in the U.S. Department of Education published in the Federal...

  1. Narrative review of models and success factors for scaling up public health interventions.

    Science.gov (United States)

    Milat, Andrew J; Bauman, Adrian; Redman, Sally

    2015-08-12

    To maximise the impact of public health research, research interventions found to be effective in improving health need to be scaled up and delivered on a population-wide basis. Theoretical frameworks and approaches are useful for describing and understanding how effective interventions are scaled up from small trials into broader policy and practice and can be used as a tool to facilitate effective scale-up. The purpose of this literature review was to synthesise evidence on scaling up public health interventions into population-wide policy and practice, with a focus on the defining and describing frameworks, processes and methods of scaling up public health initiatives. The review involved keyword searches of electronic databases including MEDLINE, CINAHL, PsycINFO, EBM Reviews and Google Scholar between August and December 2013. Keywords included 'scaling up' and 'scalability', while the search terms 'intervention research', 'translational research', 'research dissemination', 'health promotion' and 'public health' were used to focus the search on public health approaches. Studies included in the review were published in English from January 1990 to December 2013 and described processes, theories or frameworks associated with scaling up public health and health promotion interventions. There is a growing body of literature describing frameworks for scaling health interventions, with the review identifying eight frameworks, the majority of which have an explicit focus on scaling up health action in low and middle income country contexts. Key success factors for scaling up included the importance of establishing monitoring and evaluation systems, costing and economic modelling of intervention approaches, active engagement of a range of implementers and the target community, tailoring the scaled-up approach to the local context, the use of participatory approaches, the systematic use of evidence, infrastructure to support implementation, strong leadership and

  2. 'Scaling-up is a craft not a science': Catalysing scale-up of health innovations in Ethiopia, India and Nigeria.

    Science.gov (United States)

    Spicer, Neil; Bhattacharya, Dipankar; Dimka, Ritgak; Fanta, Feleke; Mangham-Jefferies, Lindsay; Schellenberg, Joanna; Tamire-Woldemariam, Addis; Walt, Gill; Wickremasinghe, Deepthi

    2014-11-01

    Donors and other development partners commonly introduce innovative practices and technologies to improve health in low and middle income countries. Yet many innovations that are effective in improving health and survival are slow to be translated into policy and implemented at scale. Understanding the factors influencing scale-up is important. We conducted a qualitative study involving 150 semi-structured interviews with government, development partners, civil society organisations and externally funded implementers, professional associations and academic institutions in 2012/13 to explore scale-up of innovative interventions targeting mothers and newborns in Ethiopia, the Indian state of Uttar Pradesh and the six states of northeast Nigeria, which are settings with high burdens of maternal and neonatal mortality. Interviews were analysed using a common analytic framework developed for cross-country comparison and themes were coded using Nvivo. We found that programme implementers across the three settings require multiple steps to catalyse scale-up. Advocating for government to adopt and finance health innovations requires: designing scalable innovations; embedding scale-up in programme design and allocating time and resources; building implementer capacity to catalyse scale-up; adopting effective approaches to advocacy; presenting strong evidence to support government decision making; involving government in programme design; invoking policy champions and networks; strengthening harmonisation among external programmes; aligning innovations with health systems and priorities. Other steps include: supporting government to develop policies and programmes and strengthening health systems and staff; promoting community uptake by involving media, community leaders, mobilisation teams and role models. We conclude that scale-up has no magic bullet solution - implementers must embrace multiple activities, and require substantial support from donors and governments in

  3. Cellular Scaling Rules for Primate Spinal Cords

    OpenAIRE

    Burish, Mark J.; Peebles, J. Klint; Baldwin, Mary K.; Tavares, Luciano; Kaas, Jon H.; Herculano-Houzel, Suzana

    2010-01-01

    The spinal cord can be considered a major sensorimotor interface between the body and the brain. How does the spinal cord scale with body and brain mass, and how are its numbers of neurons related to the number of neurons in the brain across species of different body and brain sizes? Here we determine the cellular composition of the spinal cord in eight primate species and find that its number of neurons varies as a linear function of cord length, and accompanies body mass raised to an expone...

  4. Evolutionary Glycomics: Characterization of Milk Oligosaccharides in Primates

    Science.gov (United States)

    Tao, Nannan; Wu, Shuai; Kim, Jaehan; An, Hyun Joo; Hinde, Katie; Power, Michael L.; Gagneux, Pascal; German, J. Bruce; Lebrilla, Carlito B.

    2011-01-01

    Free oligosaccharides are abundant components of mammalian milk and have primary roles as prebiotic compounds, in immune defense, and in brain development. Mass spectrometry-based technique is applied to profile milk oligosaccharides from apes (chimpanzee, gorilla, and siamang), new world monkeys (golden lion tamarin and common marmoset), and an old world monkey (rhesus). The purpose of this study was to evaluate the patterns of primate milk oligosaccharide composition from a phylogenetic perspective in order to assess the extent to which the compositions of hMOs derives from ancestral, primate patterns as opposed to more recent evolutionary events. Milk oligosaccharides were quantitated by nanoflow liquid chromatography on chip-based devices. The relative abundances of fucosylated and sialylated milk oligosaccharides in primates were also determined. For a systematic and comprehensive study of evolutionary patterns of milk oligosaccharides, cluster analysis of primate milk was performed using the chromatographic profile. In general, the oligosaccharides in primate milk, including humans, are more complex and exhibit greater diversity compared to the ones in non-primate milk. A detailed comparison of the oligosaccharides across evolution revealed non-sequential developmental pattern, i.e. that primate milk oligosaccharides do not necessarily cluster according to the primate phylogeny. This report represents the first comprehensive and quantitative effort to profile and elucidate the structures of free milk oligosaccharides so that they can be related to glycan function in different primates. PMID:21214271

  5. Scaling up community mobilisation through women's groups for maternal and neonatal health: experiences from rural Bangladesh

    Directory of Open Access Journals (Sweden)

    Nahar Tasmin

    2012-01-01

    Full Text Available Abstract Background Program coverage is likely to be an important determinant of the effectiveness of community interventions to reduce neonatal mortality. Rigorous examination and documentation of methods to scale-up interventions and measure coverage are scarce, however. To address this knowledge gap, this paper describes the process and measurement of scaling-up coverage of a community mobilisation intervention for maternal, child and neonatal health in rural Bangladesh and critiques this real-life experience in relation to available literature on scaling-up. Methods Scale-up activities took place in nine unions in rural Bangladesh. Recruitment and training of those who deliver the intervention, communication and engagement with the community and other stakeholders and active dissemination of intervention activities are described. Process evaluation and population survey data are presented and used to measure coverage and the success of scale-up. Results The intervention was scaled-up from 162 women's groups to 810, representing a five-fold increase in population coverage. The proportion of women of reproductive age and pregnant women who were engaged in the intervention increased from 9% and 3%, respectively, to 23% and 29%. Conclusions Examination and documentation of how scaling-up was successfully initiated, led, managed and monitored in rural Bangladesh provide a deeper knowledge base and valuable lessons. Strong operational capabilities and institutional knowledge of the implementing organisation were critical to the success of scale-up. It was possible to increase community engagement with the intervention without financial incentives and without an increase in managerial staff. Monitoring and feedback systems that allow for periodic programme corrections and continued innovation are central to successful scale-up and require programmatic and operational flexibility.

  6. Rethinking primate origins again.

    Science.gov (United States)

    Sussman, Robert W; Tab Rasmussen, D; Raven, Peter H

    2013-02-01

    In 1974, Cartmill introduced the theory that the earliest primate adaptations were related to their being visually oriented predators active on slender branches. Given more recent data on primate-like marsupials, nocturnal prosimians, and early fossil primates, and the context in which these primates first appeared, this theory has been modified. We hypothesize that our earliest primate relatives were likely exploiting the products of co-evolving angiosperms, along with insects attracted to fruits and flowers, in the slender supports of the terminal branch milieu. This has been referred to as the primate/angiosperm co-evolution theory. Cartmill subsequently posited that: "If the first euprimates had grasping feet and blunt teeth adapted for eating fruit, but retained small divergent orbits…" then the angiosperm coevolution theory would have support. The recent discovery of Carpolestes simpsoni provides this support. In addition, new field data on small primate diets, and a new theory concerning the visual adaptations of primates, have provided further evidence supporting the angiosperm coevolution theory. © 2012 Wiley Periodicals, Inc.

  7. Property in Nonhuman Primates

    Science.gov (United States)

    Brosnan, Sarah F.

    2011-01-01

    Property is rare in most nonhuman primates, most likely because their lifestyles are not conducive to it. Nonetheless, just because these species do not frequently maintain property does not mean that they lack the propensity to do so. Primates show respect for possession, as well as behaviors related to property, such as irrational decision…

  8. Primates, computation, and the path to language. Reply to comments on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain"

    Science.gov (United States)

    Arbib, Michael A.

    2016-03-01

    The target article [6], henceforth TA, had as its main title Towards a Computational Comparative Neuroprimatology. This unpacks into three claims: Comparative Primatology: If one wishes to understand the behavior of any one primate species (whether monkey, ape or human - TA did not discuss, e.g., lemurs but that study could well be of interest), one will gain new insight by comparing behaviors across species, sharpening one's analysis of one class of behaviors by analyzing similarities and differences between two or more species.

  9. Changing cost of HIV interventions in the context of scaling-up in India

    National Research Council Canada - National Science Library

    Dandona, Lalit; Kumar, Sg Prem; Ramesh, Yk; Rao, M Chalapathi; Kumar, A Anod; Marseille, Elliot; Kahn, James G; Dandona, Rakhi

    2008-01-01

    A rapid scaling up of HIV interventions in India is anticipated, but systematic information on how costs of HIV interventions change over time and programme scale is not available to inform planning...

  10. A Route to Scale Up DNA Origami Using DNA Tiles as Folding Staples

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Zhao; Yan, Hao; Liu, Yan

    2010-01-26

    A new strategy is presented to scale up DNA origami using multi-helical DNA tiles as folding staples. Atomic force microscopy images demonstrate the two-dimensional structures formed by using this strategy.

  11. Metabolic Profiling of Geobacter sulfurreducens during Industrial Bioprocess Scale-Up

    National Research Council Canada - National Science Library

    Muhamadali, Howbeer; Xu, Yun; Ellis, David I; Allwood, J William; Rattray, Nicholas J W; Correa, Elon; Alrabiah, Haitham; Lloyd, Jonathan R; Goodacre, Royston

    2015-01-01

    During the industrial scale-up of bioprocesses it is important to establish that the biological system has not changed significantly when moving from small laboratory-scale shake flasks or culturing...

  12. Methodologies Used for Scaling-up From a Single Energy Production Unit to State Energy Sector

    Science.gov (United States)

    Cimdina, Ginta; Timma, Lelde; Veidenbergs, Ivars; Blumberga, Dagnija

    2015-12-01

    In a well-functioning and sustainable national energy sector, each of its elements should function with maximum efficiency. To ensure maximum efficiency and study possible improvement of the sector, a scaling-up framework is presented in this work. The scaling-up framework means that the starting point is a CHP unit and its operation, the next step of aggregation is in a district heating network, followed by a municipal energy plan and finally leading to a low carbon strategy. In this framework the authors argue, that the successful, innovative practices developed and tested at the lower level of aggregation can be then transferred to the upper levels of aggregation, thus leading to a scaling-up effect of innovative practices. The work summarizes 12 methodologies used in the energy sector, by dividing these methodologies among the levels of aggregation in a scaling-up framework.

  13. Gel compression considerations for chromatography scale-up for protein C purification.

    Science.gov (United States)

    He, W; Bruley, D F; Drohan, W N

    1998-01-01

    This work is to establish theoretical and experimental relationships for the scale-up of Immobilized Metal Affinity Chromatography (IMAC) and Immuno Affinity Chromatography for the low cost production of large quantities of Protein C. The external customer requirements for this project have been established for Protein C deficient people with the goal of providing prophylactic patient treatment. Deep vein thrombosis is the major symptom for protein C deficiency creating the potential problem of embolism transport to important organs, such as, lung and brain. Gel matrices for protein C separation are being analyzed to determine the relationship between the material properties of the gel and the column collapse characteristics. The fluid flow rate and pressure drop is being examined to see how they influence column stability. Gel packing analysis includes two considerations; one is bulk compression due to flow rate, and the second is gel particle deformation due to fluid flow and pressure drop. Based on the assumption of creeping flow, Darcy's law is being applied to characterize the flow through the gel particles. Biot's mathematical description of three-dimensional consolidation in porous media is being used to develop a set of system equations. Finite difference methods are being utilized to obtain the equation solutions. In addition, special programs such as finite element approaches, ABAQUS, will be studied to determine their application to this particular problem. Experimental studies are being performed to determine flow rate and pressure drop correlation for the chromatographic columns with appropriate gels. Void fraction is being measured using pulse testing to allow Reynolds number calculations. Experimental yield stress is being measured to compare with the theoretical calculations. Total Quality Management (TQM) tools have been utilized to optimize this work. For instance, the "Scatter Diagram" has been used to evaluate and select the appropriate gels and

  14. Scaling up success to improve health: Towards a rapid assessment guide for decision makers

    Directory of Open Access Journals (Sweden)

    Jason Paltzer

    2015-01-01

    Full Text Available Introduction Evidence-based health interventions exist and are effectively implemented throughout resource-limited settings. The literature regarding scale-up strategies and frameworks is growing. The purpose of this paper is to identify and systematically document the variation in scale-up strategies to develop a rapid assessment tool for decision-makers looking to identify the most appropriate strategy for their organizational and environmental contexts. Methods A list of scale-up strategies and frameworks were identified through an in-depth literature review and conversations with scale-up and quality improvement leaders. The literature search included a broad range of terms that might be used interchangeably with scale-up of best practices. Terms included: implementation research, knowledge translation, translational research, quality improvement research, health systems improvement, scale-up, best practices, improvement collaborative, and community based research. Based on this research, 18 strategies and frameworks were identified, and nine met our inclusion criteria for scale-up of health-related strategies. We interviewed the key contact for four of the nine strategies to obtain additional information regarding the strategy’s scale-up components, targets, underlying theories, evaluation efforts, facilitating factors, and barriers. A comparative analysis of common elements and strategy characteristics was completed by two of the authors on the nine selected strategies. Key strategy characteristics and common factors that facilitate or hinder the strategy’s success in scaling up health-related interventions were identified. Results Common features of scale-up strategies include: 1 the development of context-specific evidence; 2 collaborative partnerships; 3 iterative processes; and 4 shared decision-making. Facilitating factors include strong leadership, community engagement, communication, government collaboration, and a focus on

  15. Methodologies Used for Scaling-up From a Single Energy Production Unit to State Energy Sector

    National Research Council Canada - National Science Library

    Ginta Cimdina; Lelde Timma; Ivars Veidenbergs; Dagnija Blumberga

    2015-01-01

    ... leading to a low carbon strategy. In this framework the authors argue, that the successful, innovative practices developed and tested at the lower level of aggregation can be then transferred to the upper levels of aggregation, thus leading to a scaling-up effect of innovative practices. The work summarizes 12 methodologies used in the energy sector, by dividing these methodologies among the levels of aggregation in a scaling-up framework.

  16. Quality Assessment of Physical and Organoleptic Instant Corn Rice on Scale-Up Process

    Science.gov (United States)

    Kumalasari, R.; Ekafitri, R.; Indrianti, N.

    2017-12-01

    Development of instant corn rice product has been successfully conducted on a laboratory scale. Corn has high carbohydrate content but low in fiber. The addition of fiber in instant corn rice, intended to improve the functioning of the product, and replace fiber loss during the process. Scale up process of Instant corn rice required to increase the production capacity. Scale up was the process to get identic output on a larger scale based on predetermined production scale. This study aimed to assess the changes and differences in the quality of instant corn rice during scale up. Instant corn rice scale up was done on production capacity 3 kg, 4 kg and 5 kg. Results showed that scale up of instant corn rice producing products with rehydration ratio ranges between 514% - 570%, the absorption rate ranged between 414% - 470%, swelling rate ranging between 119% - 134%, bulk density ranged from 0.3661 to 0.4745 (g/ml) and porosity ranging between 30-37%. The physical quality of instant corn rice on scale up were stable from the ones at laboratory scale on swelling rate, rehydration ratio, and absorption rate but not stable on bulk density and porosity. Organoleptic qualities were stable at increased scale compared on a laboratory scale. Bulk density was higher than those at laboratory scale, and the porosity was lower than those at laboratory scale.

  17. Primate cranial diversity.

    Science.gov (United States)

    Fleagle, John G; Gilbert, Christopher C; Baden, Andrea L

    2010-08-01

    Many studies in primate and human evolution focus on aspects of cranial morphology to address issues of systematics, phylogeny, and functional anatomy. However, broad analyses of cranial diversity within Primates as an Order are notably absent. In this study, we present a 3D geometric morphometric analysis of primate cranial morphology, providing a multivariate comparison of the major patterns of cranial shape change during primate evolution and quantitative assessments of cranial diversity among different clades. We digitized a set of 18 landmarks designed to capture overall cranial shape on male and female crania representing 66 genera of living primates. The landmark data were aligned using a Generalized Procrustes Analysis and then subjected to a principal components analysis to identify the major axes of cranial variation. Cranial diversity among clades was compared using multivariate measurements of variance. The first principal component axis reflects differences in cranial flexion, orbit size and orientation, and relative neurocranial volume. In general, it separates strepsirrhines from anthropoids. The second axis reflects differences in relative cranial height and snout length and primarily describes differences among anthropoids. Eulemur, Mandrillus, Pongo, and Homo are among the extremes in cranial shape. Anthropoids, catarrhines, and haplorhines show a higher variance than prosimians or strepsirrhines. Hominoids show the highest variance in cranial shape among extant primate clades, and much of this diversity is driven by the unique cranium of Homo sapiens. Copyright 2010 Wiley-Liss, Inc.

  18. Preparation and scale up of extended-release tablets of bromopride

    Directory of Open Access Journals (Sweden)

    Guilherme Neves Ferreira

    2014-04-01

    Full Text Available Reproducibility of the tablet manufacturing process and control of its pharmaceutics properties depends on the optimization of formulation aspects and process parameters. Computer simulation such as Design of Experiments (DOE can be used to scale up the production of this formulation, in particular for obtaining sustained-release tablets. Bromopride formulations are marketed in the form of extended-release pellets, which makes the product more expensive and difficult to manufacture. The aim of this study was to formulate new bromopride sustained release formulations as tablets, and to develop mathematical models to standardize the scale up of this formulation, controlling weight and hardness of the tablets during manufacture according to the USP 34th edition. DOE studies were conducted using Minitab(tm software. Different excipient combinations were evaluated in order to produce bromopride sustained-release matrix tablets. In the scale-up study, data were collected and variations in tableting machine parameters were measured. Data were processed by Minitab(tm software, generating mathematical equations used for prediction of powder compaction behavior, according to the settings of the tableting machine suitable for scale-up purposes. Bromopride matrix tablets with appropriate characteristics for sustained release were developed. The scale-up of the formulation with the most suitable sustained release profile was established by using mathematical models, indicating that the formulation can be a substitute for the pellets currently marketed.

  19. Scale up of services for mental health in low-income and middle-income countries.

    Science.gov (United States)

    Eaton, Julian; McCay, Layla; Semrau, Maya; Chatterjee, Sudipto; Baingana, Florence; Araya, Ricardo; Ntulo, Christina; Thornicroft, Graham; Saxena, Shekhar

    2011-10-29

    Mental disorders constitute a huge global burden of disease, and there is a large treatment gap, particularly in low-income and middle-income countries. One response to this issue has been the call to scale up mental health services. We assess progress in scaling up such services worldwide using a systematic review of literature and a survey of key national stakeholders in mental health. The large number of programmes identified suggested that successful strategies can be adopted to overcome barriers to scaling up, such as the low priority accorded to mental health, scarcity of human and financial resources, and difficulties in changing poorly organised services. However, there was a lack of well documented examples of services that had been taken to scale that could guide how to replicate successful scaling up in other settings. Recommendations are made on the basis of available evidence for how to take forward the process of scaling up services globally. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Scaling up Integrated Early Childhood Development programs: lessons from four countries.

    Science.gov (United States)

    Pérez-Escamilla, R; Cavallera, V; Tomlinson, M; Dua, T

    2018-01-01

    There is still limited knowledge regarding the translation of early child development (ECD) knowledge into effective policies and large-scale programmes. A variety of frameworks that outline the key steps in scaling up exist, but we argue that taking a complex adaptive systems (CAS) approach assists in understanding the complex, dynamic processes that result in programmes being taken to scale. The objective of this study is to examine the process of scaling up four major country-level ECD programmes through the application of a CAS framework. Nine key informants with a deep knowledge of how each ECD programme was established and brought to scale were interviewed via Skype or phone by using open-ended interviews. The interviews were tape recorded and then transcribed verbatim for subsequent coding by using CAS domains. The coding and integration of the results to identify unique and common CAS scaling up features across the case studies involved an iterative process of reaching consensus. The scaling up of all four programmes behaved as a CAS including as follows: (i) positive feedback loops (five themes) and negative feedback loops (two themes); (ii) scale-free networks (two themes); (iii) phase transitions (four themes); (iv) path dependence (two themes); and (v) emergent behaviour (six themes). Five additional themes were identified for sustainability, which was repeatedly mentioned as an important consideration when deciding how to scale up programmes. CAS analysis is likely to improve our understanding of how effective ECD programmes become scaled up. Prospective CAS implementation research is needed to continue advancing the knowledge in the field. © 2017 John Wiley & Sons Ltd.

  1. Scaling up interventions for depression in sub-Saharan Africa: lessons from Zimbabwe.

    Science.gov (United States)

    Chibanda, D; Verhey, R; Munetsi, E; Rusakaniko, S; Cowan, F; Lund, C

    2016-01-01

    There is a dearth of information on how to scale-up evidence-based psychological interventions, particularly within the context of existing HIV programs. This paper describes a strategy for the scale-up of an intervention delivered by lay health workers (LHWs) to 60 primary health care facilities in Zimbabwe. A mixed methods approach was utilized as follows: (1) needs assessment using a semi-structured questionnaire to obtain information from nurses ( n  = 48) and focus group discussions with District Health Promoters ( n  = 12) to identify key priority areas; (2) skills assessment to identify core competencies and current gaps of LHWs ( n  = 300) employed in the 60 clinics; (3) consultation workshops ( n  = 2) with key stakeholders to determine referral pathways; and (4) in-depth interviews and consultations to determine funding mechanisms for the scale-up. Five cross-cutting issues were identified as critical and needing to be addressed for a successful scale-up. These included: the lack of training in mental health, unavailability of psychiatric drugs, depleted clinical staff levels, unavailability of time for counseling, and poor and unreliable referral systems for people suffering with depression. Consensus was reached by stakeholders on supervision and support structure to address the cross-cutting issues described above and funding was successfully secured for the scale-up. Key requirements for success included early buy-in from key stakeholders, extensive consultation at each point of the scale-up journey, financial support both locally and externally, and a coherent sustainability plan endorsed by both government and private sectors.

  2. Enabling and challenging factors in institutional reform: The case of SCALE-UP

    Science.gov (United States)

    Foote, Kathleen; Knaub, Alexis; Henderson, Charles; Dancy, Melissa; Beichner, Robert J.

    2016-06-01

    While many innovative teaching strategies exist, integration into undergraduate science teaching has been frustratingly slow. This study aims to understand the low uptake of research-based instructional innovations by studying 21 successful implementations of the Student Centered Active Learning with Upside-down Pedagogies (SCALE-UP) instructional reform. SCALE-UP significantly restructures the classroom environment and pedagogy to promote highly active and interactive instruction. Although originally designed for university introductory physics courses, SCALE-UP has spread to many other disciplines at hundreds of departments around the world. This study reports findings from in-depth, open-ended interviews with 21 key contact people involved with successful secondary implementations of SCALE-UP throughout the United States. We defined successful implementations as those who restructured their pedagogy and classroom and sustained and/or spread the change. Interviews were coded to identify the most common enabling and challenging factors during reform implementation and compared to the theoretical framework of Kotter's 8-step Change Model. The most common enabling influences that emerged are documenting and leveraging evidence of local success, administrative support, interaction with outside SCALE-UP user(s), and funding. Many challenges are linked to the lack of these enabling factors including difficulty finding funding, space, and administrative and/or faculty support for reform. Our focus on successful secondary implementations meant that most interviewees were able to overcome challenges. Presentation of results is illuminated with case studies, quotes, and examples that can help secondary implementers with SCALE-UP reform efforts specifically. We also discuss the implications for policy makers, researchers, and the higher education community concerned with initiating structural change.

  3. Enabling and challenging factors in institutional reform: The case of SCALE-UP

    Directory of Open Access Journals (Sweden)

    Kathleen Foote

    2016-02-01

    Full Text Available While many innovative teaching strategies exist, integration into undergraduate science teaching has been frustratingly slow. This study aims to understand the low uptake of research-based instructional innovations by studying 21 successful implementations of the Student Centered Active Learning with Upside-down Pedagogies (SCALE-UP instructional reform. SCALE-UP significantly restructures the classroom environment and pedagogy to promote highly active and interactive instruction. Although originally designed for university introductory physics courses, SCALE-UP has spread to many other disciplines at hundreds of departments around the world. This study reports findings from in-depth, open-ended interviews with 21 key contact people involved with successful secondary implementations of SCALE-UP throughout the United States. We defined successful implementations as those who restructured their pedagogy and classroom and sustained and/or spread the change. Interviews were coded to identify the most common enabling and challenging factors during reform implementation and compared to the theoretical framework of Kotter’s 8-step Change Model. The most common enabling influences that emerged are documenting and leveraging evidence of local success, administrative support, interaction with outside SCALE-UP user(s, and funding. Many challenges are linked to the lack of these enabling factors including difficulty finding funding, space, and administrative and/or faculty support for reform. Our focus on successful secondary implementations meant that most interviewees were able to overcome challenges. Presentation of results is illuminated with case studies, quotes, and examples that can help secondary implementers with SCALE-UP reform efforts specifically. We also discuss the implications for policy makers, researchers, and the higher education community concerned with initiating structural change.

  4. Scale-up operations of CuSOB4B-NaB2BSOB4B electrolytic ...

    African Journals Online (AJOL)

    Scale-up techniques were established for an Inclined Cathode Electrochemical Cell (ICEC) for the removal of copper ions from a CuSOB4B-NaB2BSOB4B solution at reduced operation power consumption. The scale-up relationshi-ps were derived and applied in conjunction with scale-up factors. With a scale-up factor of 2, ...

  5. Primate taxonomy: species and conservation.

    Science.gov (United States)

    Rylands, Anthony B; Mittermeier, Russell A

    2014-01-01

    Primatology as a discrete branch of science involving the study of primate behavior and ecology took off in the 1960s after discovery of the importance of primates as models for biomedical research and the realization that primates provide insights into the evolutionary history of humans. Osman Hill's unfortunately incomplete monograph series on the comparative anatomy and taxonomy of the primates(1) and the Napiers' 1967 A Handbook of Living Primates(2) recorded the world's view of primate diversity at this time. This taxonomy remained the baseline for nearly three decades, with the diversity of each genus being represented by some species, but extensively as subspecies. Copyright © 2014 Wiley Periodicals, Inc.

  6. Modeling heat efficiency, flow and scale-up in the corotating disc scraped surface heat exchanger

    DEFF Research Database (Denmark)

    Friis, Alan; Szabo, Peter; Karlson, Torben

    2002-01-01

    A comparison of two different scale corotating disc scraped surface heat exchangers (CDHE) was performed experimentally. The findings were compared to predictions from a finite element model. We find that the model predicts well the flow pattern of the two CDHE's investigated. The heat transfer...... performance predicted by the model agrees well with experimental observations for the laboratory scale CDHE whereas the overall heat transfer in the scaled-up version was not in equally good agreement. The lack of the model to predict the heat transfer performance in scale-up leads us to identify the key...

  7. Numerical simulation of scale-up effects of methanol-to-olefins fluidized bed reactors

    DEFF Research Database (Denmark)

    Lu, Bona; Zhang, Jingyuan; Luo, Hao

    2017-01-01

    factors and is expected to speed up the experiment-based scale-up process with lower cost. In this study, we aim to investigate the scale-up effects through simulations of a series of methanol-to-olefins (MTO) reactors of different sizes. The two-fluid model and energy-minimization multi-scale (EMMS......)-based drag models are combined in simulations. The fluidization characteristics in terms of flow structures, velocity distribution, mass fractions of gaseous product and coke distribution are presented against available experimental data for different-sized reactors. It is found that typical hydrodynamic...

  8. Rethinking Sustainability, Scaling Up, and Enabling Environment: A Framework for Their Implementation in Drinking Water Supply

    Directory of Open Access Journals (Sweden)

    Urooj Q. Amjad

    2015-04-01

    Full Text Available The terms sustainability, scaling up, and enabling environment are inconsistently used in implementing water supply projects. To clarify these terms we develop a framework based on Normalization Process Theory, and apply the framework to a hypothetical water supply project in schools. The resulting framework provides guidance on how these terms could be implemented and analyzed in water supply projects. We conclude that effective use of the terms sustainability, scaling up, and enabling environment would focus on purpose, process, and perspective. This is the first known attempt to analyze the implementation of the three terms together in the context of water supply services.

  9. Scale-up of dextransucrase production by Leuconostoc mesenteroides in fed batch fermentation

    Directory of Open Access Journals (Sweden)

    Michelena Georgina L.

    2003-01-01

    Full Text Available Fed batch fermentation was carried out for the dextransucrase enzyme production from Leuconostoc mesenteroides and the production was scale-up using oxygen transfer criteriuom. It was found that in 5 L vessel fermentation capacity, the best agitation speed was 225 min-1 and aeration rate was 0.15 vvm, obtaining dextransucrase activity of 127 DSU/mL.. The maximum enzyme production velocity coincide with the maximum growth velocity between 6 and 7 h of fermentation, which confirmed that dextransucrase production was associated with microbial growth. High enzyme yields were achieved during scale up based on oxygen transfer rate.

  10. Scaling of cerebral blood perfusion in primates and marsupials.

    Science.gov (United States)

    Seymour, Roger S; Angove, Sophie E; Snelling, Edward P; Cassey, Phillip

    2015-08-01

    The evolution of primates involved increasing body size, brain size and presumably cognitive ability. Cognition is related to neural activity, metabolic rate and rate of blood flow to the cerebral cortex. These parameters are difficult to quantify in living animals. This study shows that it is possible to determine the rate of cortical brain perfusion from the size of the internal carotid artery foramina in skulls of certain mammals, including haplorrhine primates and diprotodont marsupials. We quantify combined blood flow rate in both internal carotid arteries as a proxy of brain metabolism in 34 species of haplorrhine primates (0.116-145 kg body mass) and compare it to the same analysis for 19 species of diprotodont marsupials (0.014-46 kg). Brain volume is related to body mass by essentially the same exponent of 0.70 in both groups. Flow rate increases with haplorrhine brain volume to the 0.95 power, which is significantly higher than the exponent (0.75) expected for most organs according to 'Kleiber's Law'. By comparison, the exponent is 0.73 in marsupials. Thus, the brain perfusion rate increases with body size and brain size much faster in primates than in marsupials. The trajectory of cerebral perfusion in primates is set by the phylogenetically older groups (New and Old World monkeys, lesser apes) and the phylogenetically younger groups (great apes, including humans) fall near the line, with the highest perfusion. This may be associated with disproportionate increases in cortical surface area and mental capacity in the highly social, larger primates. © 2015. Published by The Company of Biologists Ltd.

  11. Scaling-up of CO2 fluxes to assess carbon sequestration in rangelands of Central Asia

    Science.gov (United States)

    Bruce K. Wylie; Tagir G. Gilmanov; Douglas A. Johnson; Nicanor Z. Saliendra; Larry L. Tieszen; Ruth Anne F. Doyle; Emilio A. Laca

    2006-01-01

    Flux towers provide temporal quantification of local carbon dynamics at specific sites. The number and distribution of flux towers, however, are generally inadequate to quantify carbon fluxes across a landscape or ecoregion. Thus, scaling up of flux tower measurements through use of algorithms developed from remote sensing and GIS data is needed for spatial...

  12. An efficient permeability scaling-up technique applied to the discretized flow equations

    Energy Technology Data Exchange (ETDEWEB)

    Urgelli, D.; Ding, Yu [Institut Francais du Petrole, Rueil Malmaison (France)

    1997-08-01

    Grid-block permeability scaling-up for numerical reservoir simulations has been discussed for a long time in the literature. It is now recognized that a full permeability tensor is needed to get an accurate reservoir description at large scale. However, two major difficulties are encountered: (1) grid-block permeability cannot be properly defined because it depends on boundary conditions; (2) discretization of flow equations with a full permeability tensor is not straightforward and little work has been done on this subject. In this paper, we propose a new method, which allows us to get around both difficulties. As the two major problems are closely related, a global approach will preserve the accuracy. So, in the proposed method, the permeability up-scaling technique is integrated in the discretized numerical scheme for flow simulation. The permeability is scaled-up via the transmissibility term, in accordance with the fluid flow calculation in the numerical scheme. A finite-volume scheme is particularly studied, and the transmissibility scaling-up technique for this scheme is presented. Some numerical examples are tested for flow simulation. This new method is compared with some published numerical schemes for full permeability tensor discretization where the full permeability tensor is scaled-up through various techniques. Comparing the results with fine grid simulations shows that the new method is more accurate and more efficient.

  13. Investing in the foundation of sustainable development: pathways to scale up for early childhood development.

    Science.gov (United States)

    Richter, Linda M; Daelmans, Bernadette; Lombardi, Joan; Heymann, Jody; Boo, Florencia Lopez; Behrman, Jere R; Lu, Chunling; Lucas, Jane E; Perez-Escamilla, Rafael; Dua, Tarun; Bhutta, Zulfiqar A; Stenberg, Karin; Gertler, Paul; Darmstadt, Gary L

    2017-01-07

    Building on long-term benefits of early intervention (Paper 2 of this Series) and increasing commitment to early childhood development (Paper 1 of this Series), scaled up support for the youngest children is essential to improving health, human capital, and wellbeing across the life course. In this third paper, new analyses show that the burden of poor development is higher than estimated, taking into account additional risk factors. National programmes are needed. Greater political prioritisation is core to scale-up, as are policies that afford families time and financial resources to provide nurturing care for young children. Effective and feasible programmes to support early child development are now available. All sectors, particularly education, and social and child protection, must play a role to meet the holistic needs of young children. However, health provides a critical starting point for scaling up, given its reach to pregnant women, families, and young children. Starting at conception, interventions to promote nurturing care can feasibly build on existing health and nutrition services at limited additional cost. Failure to scale up has severe personal and social consequences. Children at elevated risk for compromised development due to stunting and poverty are likely to forgo about a quarter of average adult income per year, and the cost of inaction to gross domestic product can be double what some countries currently spend on health. Services and interventions to support early childhood development are essential to realising the vision of the Sustainable Development Goals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Including Performance Assessments in Accountability Systems: A Review of Scale-Up Efforts

    Science.gov (United States)

    Tung, Rosann

    2010-01-01

    The purpose of this literature and field review is to understand previous efforts at scaling up performance assessments for use across districts and states. Performance assessments benefit students and teachers by providing more opportunities for students to demonstrate their knowledge and complex skills, by providing teachers with better…

  15. Scaling up Evidence-Based Practices: Strategies from Investing in Innovation (i3)

    Science.gov (United States)

    DeWire, Tom; McKithen, Clarissa; Carey, Rebecca

    2017-01-01

    What can the Investing in Innovation (i3) grantees tell us about scaling innovative educational practices? The newly released white paper "Scaling Up Evidence-Based Practices: Strategies from Investing in Innovation (i3)" captures the experiences of nine grantees whose projects collectively have reached over 1.2 million students across…

  16. Electronic Government in the City of Fez, Morocco : Scaling up to the ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    In the pilot phase of the project (101980), electronic service delivery was introduced and successfully deployed in the Fez-Agdal local government office. This phase will scale up the project to include the remaining local government offices in the city of Fez. It will also upgrade, enhance and complete the automation of the ...

  17. HIV viral load scale-up: multiple interventions to meet the HIV treatment cascade.

    Science.gov (United States)

    Carmona, Sergio; Peter, Trevor; Berrie, Leigh

    2017-03-01

    In 2015, the WHO urged countries to provide ART to all people living with HIV, irrespective of their CD4 cell count, this new recommendation supports the Joint United Nations Programme on HIV/AIDS elimination targets. However, to meet these aims, urgent scale-up of viral load testing is critical. The multiple interventions in the healthcare system required to support scale-up of viral load testing are reviewed here. It is estimated that 18.2 million individuals are accessing antiretroviral therapy, consequently this will cause significant demand for viral load monitoring; however, at the current rate of implementation, demand will not meet the required target by 2020. To change this trajectory, multiple stakeholders must be involved, communities and key populations need increased treatment literacy to create demand and greater numbers of healthcare workers will require training. In addition, laboratories and point-of-care testing sites will need to be expanded, and adequate monitoring and evaluation tools will need to be put in place to identify gaps in the system, to institute prompt corrective actions and to direct resources where needed. Sufficient scale-up of viral load may well be possible if innovations in mHealth are used to support healthcare workers and patients with regard to the scale-up and effective use of viral load monitoring; new laboratory technologies are implemented, both at a centralized level and point-of-care, to manage higher volumes and improve coverage; and there is careful coordination between implementing partners and funders.

  18. 77 FR 25152 - Applications for New Awards; Investing in Innovation Fund, Scale-Up Grants

    Science.gov (United States)

    2012-04-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Applications for New Awards; Investing in Innovation Fund, Scale- Up Grants Correction In notice document 2012-7362 appearing on pages 18216-18229 in the issue of Tuesday, March 27, 2012 make the following...

  19. An Experiment to Illustrate the Hazards of Exothermic Reaction Scale-Up

    Science.gov (United States)

    Clark, William; Lei, Melinda; Kirichenko, Erika; Dickerson, Kellie; Prytko, Robert

    2017-01-01

    Exothermic reactions can present safety hazards and there is a recognized need for reaction safety education at the undergraduate level. We present an experiment that illustrates the pitfall of direct scale-up of an exothermic reaction that can lead to thermal runaway. The iodide-catalyzed hydrogen peroxide decomposition reaction yields…

  20. Scaling-up vaccine production: implementation aspects of a biomass growth observer and controller

    NARCIS (Netherlands)

    Soons, Z.I.T.A.; IJssel, van den J.; Pol, van der L.A.; Straten, van G.; Boxtel, van A.J.B.

    2009-01-01

    Abstract This study considers two aspects of the implementation of a biomass growth observer and specific growth rate controller in scale-up from small- to pilot-scale bioreactors towards a feasible bulk production process for whole-cell vaccine against whooping cough. The first is the calculation

  1. Integrated Graduate and Continuing Education in Protein Chromatography for Bioprocess Development and Scale-Up

    Science.gov (United States)

    Carta, Jungbauer

    2011-01-01

    We describe an intensive course that integrates graduate and continuing education focused on the development and scale-up of chromatography processes used for the recovery and purification of proteins with special emphasis on biotherapeutics. The course includes lectures, laboratories, teamwork, and a design exercise and offers a complete view of…

  2. Scaling up community mobilisation through women's groups for maternal and neonatal health: Experiences from rural Bangladesh

    NARCIS (Netherlands)

    T. Nahar (Tasmin); K. Azad (Kishwar); B.H. Aumon (Bedowra Haq); L. Younes (Layla); S. Shaha (Sanjit); A. Kuddus (Abdul); A. Prost (Audrey); A.J. Houweling (Tanja); A. Costello (Anthony); E. Fottrell (Edward)

    2012-01-01

    textabstractBackground: Program coverage is likely to be an important determinant of the effectiveness of community interventions to reduce neonatal mortality. Rigorous examination and documentation of methods to scale-up interventions and measure coverage are scarce, however. To address this

  3. Cost-effectiveness of scaling up voluntary counselling and testing in West-Java, Indonesia.

    Science.gov (United States)

    Tromp, Noor; Siregar, Adiatma; Leuwol, Barnabas; Komarudin, Dindin; van der Ven, Andre; van Crevel, Reinout; Baltussen, Rob

    2013-01-01

    to evaluate the costs-effectiveness of scaling up community-based VCT in West-Java. the Asian epidemic model (AEM) and resource needs model (RNM) were used to calculate incremental costs per HIV infection averted and per disability-adjusted life years saved (DALYs). Locally monitored demographic, epidemiological behavior and cost data were used as model input. scaling up community-based VCT in West-Java will reduce the overall population prevalence by 36% in 2030 and costs US$248 per HIV infection averted and US$9.17 per DALY saved. Cost-effectiveness estimation were most sensitive to the impact of VCT on condom use and to the population size of clients of female sex workers (FSWs), but were overall robust. The total costs for scaling up community-based VCT range between US$1.3 and 3.8 million per year and require the number of VCT integrated clinics at public community health centers to increase from 73 in 2010 to 594 in 2030. scaling up community-based VCT seems both an effective and cost-effective intervention. However, in order to prioritize VCT in HIV/AIDS control in West-Java, issues of budget availability and organizational capacity should be addressed.

  4. A framework for scaling up health interventions: lessons from large-scale improvement initiatives in Africa.

    Science.gov (United States)

    Barker, Pierre M; Reid, Amy; Schall, Marie W

    2016-01-29

    Scaling up complex health interventions to large populations is not a straightforward task. Without intentional, guided efforts to scale up, it can take many years for a new evidence-based intervention to be broadly implemented. For the past decade, researchers and implementers have developed models of scale-up that move beyond earlier paradigms that assumed ideas and practices would successfully spread through a combination of publication, policy, training, and example. Drawing from the previously reported frameworks for scaling up health interventions and our experience in the USA and abroad, we describe a framework for taking health interventions to full scale, and we use two large-scale improvement initiatives in Africa to illustrate the framework in action. We first identified other scale-up approaches for comparison and analysis of common constructs by searching for systematic reviews of scale-up in health care, reviewing those bibliographies, speaking with experts, and reviewing common research databases (PubMed, Google Scholar) for papers in English from peer-reviewed and "gray" sources that discussed models, frameworks, or theories for scale-up from 2000 to 2014. We then analyzed the results of this external review in the context of the models and frameworks developed over the past 20 years by Associates in Process Improvement (API) and the Institute for Healthcare improvement (IHI). Finally, we reflected on two national-scale improvement initiatives that IHI had undertaken in Ghana and South Africa that were testing grounds for early iterations of the framework presented in this paper. The framework describes three core components: a sequence of activities that are required to get a program of work to full scale, the mechanisms that are required to facilitate the adoption of interventions, and the underlying factors and support systems required for successful scale-up. The four steps in the sequence include (1) Set-up, which prepares the ground for

  5. Scaling up diarrhea prevention and treatment interventions: a Lives Saved Tool analysis.

    Science.gov (United States)

    Fischer Walker, Christa L; Friberg, Ingrid K; Binkin, Nancy; Young, Mark; Walker, Neff; Fontaine, Olivier; Weissman, Eva; Gupta, Akanksha; Black, Robert E

    2011-03-01

    Diarrhea remains a leading cause of mortality among young children in low- and middle-income countries. Although the evidence for individual diarrhea prevention and treatment interventions is solid, the effect a comprehensive scale-up effort would have on diarrhea mortality has not been estimated. We use the Lives Saved Tool (LiST) to estimate the potential lives saved if two scale-up scenarios for key diarrhea interventions (oral rehydration salts [ORS], zinc, antibiotics for dysentery, rotavirus vaccine, vitamin A supplementation, basic water, sanitation, hygiene, and breastfeeding) were implemented in the 68 high child mortality countries. We also conduct a simple costing exercise to estimate cost per capita and total costs for each scale-up scenario. Under the ambitious (feasible improvement in coverage of all interventions) and universal (assumes near 100% coverage of all interventions) scale-up scenarios, we demonstrate that diarrhea mortality can be reduced by 78% and 92%, respectively. With universal coverage nearly 5 million diarrheal deaths could be averted during the 5-year scale-up period for an additional cost of US$12.5 billion invested across 68 priority countries for individual-level prevention and treatment interventions, and an additional US$84.8 billion would be required for the addition of all water and sanitation interventions. Using currently available interventions, we demonstrate that with improved coverage, diarrheal deaths can be drastically reduced. If delivery strategy bottlenecks can be overcome and the international community can collectively deliver on the key strategies outlined in these scenarios, we will be one step closer to achieving success for the United Nations' Millennium Development Goal 4 (MDG4) by 2015.

  6. Scaling up diarrhea prevention and treatment interventions: a Lives Saved Tool analysis.

    Directory of Open Access Journals (Sweden)

    Christa L Fischer Walker

    2011-03-01

    Full Text Available BACKGROUND: Diarrhea remains a leading cause of mortality among young children in low- and middle-income countries. Although the evidence for individual diarrhea prevention and treatment interventions is solid, the effect a comprehensive scale-up effort would have on diarrhea mortality has not been estimated. METHODS AND FINDINGS: We use the Lives Saved Tool (LiST to estimate the potential lives saved if two scale-up scenarios for key diarrhea interventions (oral rehydration salts [ORS], zinc, antibiotics for dysentery, rotavirus vaccine, vitamin A supplementation, basic water, sanitation, hygiene, and breastfeeding were implemented in the 68 high child mortality countries. We also conduct a simple costing exercise to estimate cost per capita and total costs for each scale-up scenario. Under the ambitious (feasible improvement in coverage of all interventions and universal (assumes near 100% coverage of all interventions scale-up scenarios, we demonstrate that diarrhea mortality can be reduced by 78% and 92%, respectively. With universal coverage nearly 5 million diarrheal deaths could be averted during the 5-year scale-up period for an additional cost of US$12.5 billion invested across 68 priority countries for individual-level prevention and treatment interventions, and an additional US$84.8 billion would be required for the addition of all water and sanitation interventions. CONCLUSION: Using currently available interventions, we demonstrate that with improved coverage, diarrheal deaths can be drastically reduced. If delivery strategy bottlenecks can be overcome and the international community can collectively deliver on the key strategies outlined in these scenarios, we will be one step closer to achieving success for the United Nations' Millennium Development Goal 4 (MDG4 by 2015.

  7. Scaling Up Diarrhea Prevention and Treatment Interventions: A Lives Saved Tool Analysis

    Science.gov (United States)

    Walker, Christa L. Fischer; Friberg, Ingrid K.; Binkin, Nancy; Young, Mark; Walker, Neff; Fontaine, Olivier; Weissman, Eva; Gupta, Akanksha; Black, Robert E.

    2011-01-01

    Background Diarrhea remains a leading cause of mortality among young children in low- and middle-income countries. Although the evidence for individual diarrhea prevention and treatment interventions is solid, the effect a comprehensive scale-up effort would have on diarrhea mortality has not been estimated. Methods and Findings We use the Lives Saved Tool (LiST) to estimate the potential lives saved if two scale-up scenarios for key diarrhea interventions (oral rehydration salts [ORS], zinc, antibiotics for dysentery, rotavirus vaccine, vitamin A supplementation, basic water, sanitation, hygiene, and breastfeeding) were implemented in the 68 high child mortality countries. We also conduct a simple costing exercise to estimate cost per capita and total costs for each scale-up scenario. Under the ambitious (feasible improvement in coverage of all interventions) and universal (assumes near 100% coverage of all interventions) scale-up scenarios, we demonstrate that diarrhea mortality can be reduced by 78% and 92%, respectively. With universal coverage nearly 5 million diarrheal deaths could be averted during the 5-year scale-up period for an additional cost of US$12.5 billion invested across 68 priority countries for individual-level prevention and treatment interventions, and an additional US$84.8 billion would be required for the addition of all water and sanitation interventions. Conclusion Using currently available interventions, we demonstrate that with improved coverage, diarrheal deaths can be drastically reduced. If delivery strategy bottlenecks can be overcome and the international community can collectively deliver on the key strategies outlined in these scenarios, we will be one step closer to achieving success for the United Nations' Millennium Development Goal 4 (MDG4) by 2015. Please see later in the article for the Editors' Summary PMID:21445330

  8. Scaling-up NLP Pipelines to Process Large Corpora of Clinical Notes.

    Science.gov (United States)

    Divita, G; Carter, M; Redd, A; Zeng, Q; Gupta, K; Trautner, B; Samore, M; Gundlapalli, A

    2015-01-01

    This article is part of the Focus Theme of Methods of Information in Medicine on "Big Data and Analytics in Healthcare". This paper describes the scale-up efforts at the VA Salt Lake City Health Care System to address processing large corpora of clinical notes through a natural language processing (NLP) pipeline. The use case described is a current project focused on detecting the presence of an indwelling urinary catheter in hospitalized patients and subsequent catheter-associated urinary tract infections. An NLP algorithm using v3NLP was developed to detect the presence of an indwelling urinary catheter in hospitalized patients. The algorithm was tested on a small corpus of notes on patients for whom the presence or absence of a catheter was already known (reference standard). In planning for a scale-up, we estimated that the original algorithm would have taken 2.4 days to run on a larger corpus of notes for this project (550,000 notes), and 27 days for a corpus of 6 million records representative of a national sample of notes. We approached scaling-up NLP pipelines through three techniques: pipeline replication via multi-threading, intra-annotator threading for tasks that can be further decomposed, and remote annotator services which enable annotator scale-out. The scale-up resulted in reducing the average time to process a record from 206 milliseconds to 17 milliseconds or a 12- fold increase in performance when applied to a corpus of 550,000 notes. Purposely simplistic in nature, these scale-up efforts are the straight forward evolution from small scale NLP processing to larger scale extraction without incurring associated complexities that are inherited by the use of the underlying UIMA framework. These efforts represent generalizable and widely applicable techniques that will aid other computationally complex NLP pipelines that are of need to be scaled out for processing and analyzing big data.

  9. Hands of early primates.

    Science.gov (United States)

    Boyer, Doug M; Yapuncich, Gabriel S; Chester, Stephen G B; Bloch, Jonathan I; Godinot, Marc

    2013-12-01

    Questions surrounding the origin and early evolution of primates continue to be the subject of debate. Though anatomy of the skull and inferred dietary shifts are often the focus, detailed studies of postcrania and inferred locomotor capabilities can also provide crucial data that advance understanding of transitions in early primate evolution. In particular, the hand skeleton includes characteristics thought to reflect foraging, locomotion, and posture. Here we review what is known about the early evolution of primate hands from a comparative perspective that incorporates data from the fossil record. Additionally, we provide new comparative data and documentation of skeletal morphology for Paleogene plesiadapiforms, notharctines, cercamoniines, adapines, and omomyiforms. Finally, we discuss implications of these data for understanding locomotor transitions during the origin and early evolutionary history of primates. Known plesiadapiform species cannot be differentiated from extant primates based on either intrinsic hand proportions or hand-to-body size proportions. Nonetheless, the presence of claws and a different metacarpophalangeal [corrected] joint form in plesiadapiforms indicate different grasping mechanics. Notharctines and cercamoniines have intrinsic hand proportions with extremely elongated proximal phalanges and digit rays relative to metacarpals, resembling tarsiers and galagos. But their hand-to-body size proportions are typical of many extant primates (unlike those of tarsiers, and possibly Teilhardina, which have extremely large hands). Non-adapine adapiforms and omomyids exhibit additional carpal features suggesting more limited dorsiflexion, greater ulnar deviation, and a more habitually divergent pollex than observed plesiadapiforms. Together, features differentiating adapiforms and omomyiforms from plesiadapiforms indicate increased reliance on vertical prehensile-clinging and grasp-leaping, possibly in combination with predatory behaviors in

  10. Modulation of Abnormal Metabolic Brain Networks by Experimental Therapies in a Nonhuman Primate Model of Parkinson Disease: An Application to Human Retinal Pigment Epithelial Cell Implantation.

    Science.gov (United States)

    Peng, Shichun; Ma, Yilong; Flores, Joseph; Cornfeldt, Michael; Mitrovic, Branka; Eidelberg, David; Doudet, Doris J

    2016-10-01

    Abnormal covariance pattern of regional metabolism associated with Parkinson disease (PD) is modulated by dopaminergic pharmacotherapy. Using high-resolution (18)F-FDG PET and network analysis, we previously derived and validated a parkinsonism-related metabolic pattern (PRP) in nonhuman primate models of PD. It is currently not known whether this network is modulated by experimental therapeutics. In this study, we examined changes in network activity by striatal implantation of human levodopa-producing retinal pigment epithelial (hRPE) cells in parkinsonian macaques and evaluated the reproducibility of network activity in a small test-retest study. (18)F-FDG PET scans were acquired in 8 healthy macaques and 8 macaques with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced bilateral nigrostriatal dopaminergic lesions after unilateral putaminal implantation of hRPE cells or sham surgery. PRP activity was measured prospectively in all animals and in a subset of test-retest animals using a network quantification approach. Network activity and regional metabolic values were compared on a hemispheric basis between animal groups and treatment conditions. All individual macaques showed clinical improvement after hRPE cell implantation compared with the sham surgery. PRP activity was elevated in the untreated MPTP hemispheres relative to those of the normal controls (P therapy and other symptomatic interventions. With further validation in large samples, (18)F-FDG PET imaging with network analysis may provide a viable biomarker for assessing treatment response in animal models of PD after experimental therapies. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  11. A comparative neurological approach to emotional expressions in primate vocalizations.

    Science.gov (United States)

    Gruber, Thibaud; Grandjean, Didier

    2017-02-01

    Different approaches from different research domains have crystallized debate over primate emotional processing and vocalizations in recent decades. On one side, researchers disagree about whether emotional states or processes in animals truly compare to those in humans. On the other, a long-held assumption is that primate vocalizations are innate communicative signals over which nonhuman primates have limited control and a mirror of the emotional state of the individuals producing them, despite growing evidence of intentional production for some vocalizations. Our goal is to connect both sides of the discussion in deciphering how the emotional content of primate calls compares with emotional vocal signals in humans. We focus particularly on neural bases of primate emotions and vocalizations to identify cerebral structures underlying emotion, vocal production, and comprehension in primates, and discuss whether particular structures or neuronal networks solely evolved for specific functions in the human brain. Finally, we propose a model to classify emotional vocalizations in primates according to four dimensions (learning, control, emotional, meaning) to allow comparing calls across species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Quantification of Temozolomide in Nonhuman Primate Fluids by Isocratic Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry to Study Brain Tissue Penetration Following Intranasal or Intravenous Delivery

    Directory of Open Access Journals (Sweden)

    Cody J. Peer

    2016-02-01

    Full Text Available A sensitive and selective ultra-high performance liquid chromatography-tandem mass spectrometric method was developed for the quantification of temozolomide (TMZ in nonhuman primate (NHP plasma, cerebrospinal fluid (CSF, and brain extracellular fluid (ECF following microdialysis. Ethyl acetate was used to extract the plasma and CSF samples, using theophylline as the internal standard (IS. ECF samples were diluted with acetonitrile prior to analysis. TMZ was separated on a Waters UPLC® BEH C18 column with an isocratic mobile phase of ammonium acetate (10 mM-0.1% formic acid/acetonitrile (30:70, v/v in a positive-ion multiple reaction monitoring mode (m/z 195.5→137.6 for TMZ; m/z 181.5→124.2 for IS. The retention time of TMZ and theophylline was 0.45 min with a total run time of 2.5 min. The method was validated over the range from 5–2000 ng/mL in NHP plasma, CSF, and ECF with respect to linearity, accuracy, precision, selectivity, and stability. This method was successfully applied toward the measurement of pharmacokinetic samples following various routes of drug administration.

  13. Dopamine D1 receptor imaging in the rodent and primate brain using the isoquinoline (+)-[{sup 11}C]A-69024 and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Besret, L.; Herard, A.S.; Guillermier, M.; Hantraye, P. [CNRS, URA 2210, F-91406 Orsay (France); Dolle, F.; Demphel, S.; Hinnen, F.; Coulon, C.; Ottaviani, M.; Bottlaender, M. [CEA, DSV, I2BM, SHFJ, Lab Imagerie Mol Expt, F-91406 Orsay (France); Herard, A.S.; Guillermier, M.; Hantraye, P. [CEA, DSV, I2BM, Mol Imaging Res Ctr, F-92265 Fontenay Aux Roses (France); Kassiou, M. [Univ Sydney, Discipline Med Radiat Sci, Sydney, NSW 2006 (Australia); Kassiou, M. [Univ Sydney, Brain and Mind Res Inst, Sydney, NSW 2050 (Australia); Kassiou, M. [Univ Sydney, Sch Chem, Sydney, NSW 2006 (Australia)

    2008-07-01

    In vivo pharmacokinetic and brain binding characteristics of (+)-[{sup 11}C]A-69024, a high-affinity-D1-selective dopamine receptor antagonist, were assessed with micro-PET and {beta}-microprobes in the rat and PET in the baboon. The biodistribution of (+)-[{sup 11}C]A-69024 in rats and baboons showed a rapid brain uptake (reaching a maximal value at 5 and 15 min postinjection in rats and baboons, respectively), followed by a slow wash out. The region/cerebellum concentration ratio was characterized by a fourfold higher uptake in striatum and a twofold higher uptake in cortical regions, consistent with in vivo specific binding of the radiotracer in these cerebral regions. Furthermore, this specific (+)-[{sup 11}C]A-69024 binding significantly correlated with the reported in vitro distribution of dopamine D1-receptors. Finally, the specific uptake of the tracer in the striatum and cortical regions was completely prevented by either a pretreatment with large doses of nonradioactive {+-}A-69024 or of the D1-selective antagonist SCH23390, resulting in a similar uptake in the reference region (cerebellum) and in other brain regions. Thus, (+)-[{sup 11}C]A-69024 appears to be a specific and enantioselective radioligand to visualize and quantify brain dopamine D1 receptors in vivo using positron emission tomography. (authors)

  14. Pre-clinical testing of a phased array ultrasound system for MRI-guided noninvasive surgery of the brain-A primate study

    Energy Technology Data Exchange (ETDEWEB)

    Hynynen, Kullervo [Department of Radiology, Brigham and Women' s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115 (United States)]. E-mail: kullervo@bwh.harvard.edu; McDannold, Nathan [Department of Radiology, Brigham and Women' s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115 (United States); Clement, Greg [Department of Radiology, Brigham and Women' s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115 (United States); Jolesz, Ferenc A. [Department of Radiology, Brigham and Women' s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115 (United States); Zadicario, Eyal [InSightec, Inc., Haifa (Israel); Killiany, Ron [Boston University, Boston, MA (United States); Moore, Tara [Boston University, Boston, MA (United States); Rosen, Douglas [Boston University, Boston, MA (United States)

    2006-08-15

    MRI-guided and monitored focused ultrasound thermal surgery of brain through intact skull was tested in three rhesus monkeys. The aim of this study was to determine the amount of skull heating in an animal model with a head shape similar to that of a human. The ultrasound beam was generated by a 512 channel phased array system (Exablate[reg] 3000, InSightec, Haifa, Israel) that was integrated within a 1.5-T MR-scanner. The skin was pre-cooled by degassed temperature controlled water circulating between the array surface and the skin. Skull surface temperature was measured with invasive thermocouple probes. The results showed that by applying surface cooling the skin and skull surface can be protected, and that the brain surface temperature becomes the limiting factor. The MRI thermometry was shown to be useful in detecting the tissue temperature distribution next to the bone, and it should be used to monitor the brain surface temperature. The acoustic intensity values during the 20 s sonications were adequate for thermal ablation in the human brain provided that surface cooling is used.

  15. Evidence-based adaptation and scale-up of a mobile phone health information service.

    Science.gov (United States)

    L'Engle, Kelly; Plourde, Kate F; Zan, Trinity

    2017-01-01

    The research base recommending the use of mobile phone interventions for health improvement is growing at a rapid pace. The use of mobile phones to deliver health behavior change and maintenance interventions in particular is gaining a robust evidence base across geographies, populations, and health topics. However, research on best practices for successfully scaling mHealth interventions is not keeping pace, despite the availability of frameworks for adapting and scaling health programs. m4RH-Mobile for Reproductive Health-is an SMS, or text message-based, health information service that began in two countries and over a period of 7 years has been adapted and scaled to new population groups and new countries. Success can be attributed to following key principles for scaling up health programs, including continuous stakeholder engagement; ongoing monitoring, evaluation, and research including extensive content and usability testing with the target audience; strategic dissemination of results; and use of marketing and sustainability principles for social initiatives. This article investigates how these factors contributed to vertical, horizontal, and global scale-up of the m4RH program. Vertical scale of m4RH is demonstrated in Tanzania, where the early engagement of stakeholders including the Ministry of Health catalyzed expansion of m4RH content and national-level program reach. Ongoing data collection has provided real-time data for decision-making, information about the user base, and peer-reviewed publications, yielding government endorsement and partner hand-off for sustainability of the m4RH platform. Horizontal scale-up and adaptation of m4RH has occurred through expansion to new populations in Rwanda, Uganda, and Tanzania, where best practices for design and implementation of mHealth programs were followed to ensure the platform meets the needs of target populations. m4RH also has been modified and packaged for global scale-up through licensing and toolkit

  16. Evidence-based adaptation and scale-up of a mobile phone health information service

    Science.gov (United States)

    Plourde, Kate F.; Zan, Trinity

    2017-01-01

    Background The research base recommending the use of mobile phone interventions for health improvement is growing at a rapid pace. The use of mobile phones to deliver health behavior change and maintenance interventions in particular is gaining a robust evidence base across geographies, populations, and health topics. However, research on best practices for successfully scaling mHealth interventions is not keeping pace, despite the availability of frameworks for adapting and scaling health programs. Methods m4RH—Mobile for Reproductive Health—is an SMS, or text message-based, health information service that began in two countries and over a period of 7 years has been adapted and scaled to new population groups and new countries. Success can be attributed to following key principles for scaling up health programs, including continuous stakeholder engagement; ongoing monitoring, evaluation, and research including extensive content and usability testing with the target audience; strategic dissemination of results; and use of marketing and sustainability principles for social initiatives. This article investigates how these factors contributed to vertical, horizontal, and global scale-up of the m4RH program. Results Vertical scale of m4RH is demonstrated in Tanzania, where the early engagement of stakeholders including the Ministry of Health catalyzed expansion of m4RH content and national-level program reach. Ongoing data collection has provided real-time data for decision-making, information about the user base, and peer-reviewed publications, yielding government endorsement and partner hand-off for sustainability of the m4RH platform. Horizontal scale-up and adaptation of m4RH has occurred through expansion to new populations in Rwanda, Uganda, and Tanzania, where best practices for design and implementation of mHealth programs were followed to ensure the platform meets the needs of target populations. m4RH also has been modified and packaged for global scale-up

  17. Scaling-up treatment of depression and anxiety: a global return on investment analysis.

    Science.gov (United States)

    Chisholm, Dan; Sweeny, Kim; Sheehan, Peter; Rasmussen, Bruce; Smit, Filip; Cuijpers, Pim; Saxena, Shekhar

    2016-05-01

    Depression and anxiety disorders are highly prevalent and disabling disorders, which result not only in an enormous amount of human misery and lost health, but also lost economic output. Here we propose a global investment case for a scaled-up response to the public health and economic burden of depression and anxiety disorders. In this global return on investment analysis, we used the mental health module of the OneHealth tool to calculate treatment costs and health outcomes in 36 countries between 2016 and 2030. We assumed a linear increase in treatment coverage. We factored in a modest improvement of 5% in both the ability to work and productivity at work as a result of treatment, subsequently mapped to the prevailing rates of labour participation and gross domestic product (GDP) per worker in each country. The net present value of investment needed over the period 2016-30 to substantially scale up effective treatment coverage for depression and anxiety disorders is estimated to be US$147 billion. The expected returns to this investment are also substantial. In terms of health impact, scaled-up treatment leads to 43 million extra years of healthy life over the scale-up period. Placing an economic value on these healthy life-years produces a net present value of $310 billion. As well as these intrinsic benefits associated with improved health, scaled-up treatment of common mental disorders also leads to large economic productivity gains (a net present value of $230 billion for scaled-up depression treatment and $169 billion for anxiety disorders). Across country income groups, resulting benefit to cost ratios amount to 2·3-3·0 to 1 when economic benefits only are considered, and 3·3-5·7 to 1 when the value of health returns is also included. Return on investment analysis of the kind reported here can contribute strongly to a balanced investment case for enhanced action to address the large and growing burden of common mental disorders worldwide. Grand

  18. Kinetic modeling of [18 F]VAT, a novel radioligand for PET imaging vesicular acetylcholine transporter (VAChT) in nonhuman primate brain.

    Science.gov (United States)

    Jin, Hongjun; Yue, Xuyi; Liu, Hui; Han, Junbin; Flores, Hubert; Su, Yi; Parsons, Stanley M; Perlmutter, Joel S; Tu, Zhude

    2018-01-06

    Molecular imaging of vesicular acetylcholine transporter (VAChT) in the brain provides an important cholinergic biomarker for the pathophysiology and treatment of dementias including Alzheimer's disease (AD). In this study, kinetics modeling methods were applied and compared for quantifying regional brain uptake of the VAChT-specific PET radiotracer, ((-)-(1-(-8-(2-fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(4-fluorophenyl)-methanone) ([18 F]VAT) in macaques. Total volume distribution (VT ) estimates were compared for one-tissue compartment model (1TCM), two-tissue compartment model (2TCM), Logan graphic analysis (LoganAIF) and multiple linear analysis (MA1) with arterial blood input function using data from three macaques. Using the cerebellum-hemispheres as the reference region with data from seven macaques, three additional models were compared: reference tissue model (RTM), simplified reference tissue model (SRTM), and Logan graphic analysis (LoganREF). Model selection criterion (MSC) indicated that a) 2TCM and SRTM were the most appropriate kinetics models for [18 F]VAT; and b) SRTM was strongly correlated with 2TCM (Pearson's coefficients r > 0.93, p VAT has good reproducibility and reliability (TRV 0.72). These studies demonstrate [18 F]VAT is a promising VAChT PET tracer for quantitative assessment of VAChT levels in the brain of living subjects. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. Pore-Water Extraction Scale-Up Study for the SX Tank Farm

    Energy Technology Data Exchange (ETDEWEB)

    Truex, Michael J.; Oostrom, Martinus; Wietsma, Thomas W.; Last, George V.; Lanigan, David C.

    2013-01-15

    The phenomena related to pore-water extraction from unsaturated sediments have been previously examined with limited laboratory experiments and numerical modeling. However, key scale-up issues have not yet been addressed. Laboratory experiments and numerical modeling were conducted to specifically examine pore-water extraction for sediment conditions relevant to the vadose zone beneath the SX Tank Farm at Hanford Site in southeastern Washington State. Available SX Tank Farm data were evaluated to generate a conceptual model of the subsurface for a targeted pore-water extraction application in areas with elevated moisture and Tc-99 concentration. The hydraulic properties of the types of porous media representative of the SX Tank Farm target application were determined using sediment mixtures prepared in the laboratory based on available borehole sediment particle size data. Numerical modeling was used as an evaluation tool for scale-up of pore-water extraction for targeted field applications.

  20. Voluntary medical male circumcision: an introduction to the cost, impact, and challenges of accelerated scaling up.

    Directory of Open Access Journals (Sweden)

    Catherine Hankins

    2011-11-01

    Full Text Available Scaling up voluntary medical male circumcision (VMMC for HIV prevention is cost saving and creates fiscal space in the future that otherwise would have been encumbered by antiretroviral treatment costs. An investment of US$1,500,000,000 between 2011 and 2015 to achieve 80% coverage in 13 priority countries in southern and eastern Africa will result in net savings of US$16,500,000,000. Strong political leadership, country ownership, and stakeholder engagement, along with effective demand creation, community mobilisation, and human resource deployment, are essential. This collection of articles on determining the cost and impact of VMMC for HIV prevention signposts the way forward to scaling up VMMC service delivery safely and efficiently to reap individual- and population-level benefits.

  1. Reduction in extrapulmonary tuberculosis in context of antiretroviral therapy scale-up in rural South Africa.

    Science.gov (United States)

    Hoogendoorn, J C; Ranoto, L; Muditambi, N; Railton, J; Maswanganyi, M; Struthers, H E; McIntyre, J A; Peters, R P H

    2017-09-01

    Scale-up of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection has reduced the incidence of pulmonary tuberculosis (PTB) in South Africa. Despite the strong association of HIV infection with extrapulmonary tuberculosis (EPTB), the effect of ART on the epidemiology of EPTB remains undocumented. We conducted a retrospective record review of patients initiated on treatment for EPTB in 2009 (ART coverage EPTB (n = 399 in 2009 vs. 336 in 2013; P EPTB cases, the proportion of miliary TB and disseminated TB decreased significantly (both P EPTB cases that is similar to that of PTB in the context of the ART scale-up. The changing profile of EPTB warrants attention of healthcare workers.

  2. Nb3Sn accelerator magnet technology scale up based on cos-theta coils

    Energy Technology Data Exchange (ETDEWEB)

    Nobrega, F.; Ambrosio, G.; Andreev, N.; Barzi, E.; Bossert, R.; Carcagno, R.; Feher, S.; Kashikhin, V.S.; Kashikhin, V.V.; Lamm, M.J.; Novitski, I.; Pischalnikov, Yu.; Sylvester, C.; Tartaglia, M.; Turrioni, D.; Yamada, R.; Zlobin, A.V.; /Fermilab

    2006-08-01

    After successful testing of a 1 m long dipole mirror magnet and three dipole models based on two-layer Nb{sub 3}Sn coils, Fermilab has started a Nb{sub 3}Sn technology scale-up program using the dipole mirror design and the developed Nb{sub 3}Sn coil fabrication technology based on the wind-and-react method. The scale-up will be performed in several steps starting from a 2 m long coil made of Powder-in-Tube (PIT) strand. This will be followed by 4 m long Nb{sub 3}Sn coils made of PIT and RRP strands that will be fabricated into dipole mirror magnets and tested. This paper presents a summary of Fermilab's wind-and-react short model program. It includes details on the 2 m and 4 m long, 2 layer Nb{sub 3}Sn dipole mirror magnet design, mechanical structure, and fabrication infrastructure.

  3. Scale-up of wet kneading in a novel vertical high shear kneader.

    Science.gov (United States)

    Watano, Satoru; Okamoto, Takumi; Sato, Yoshinobu; Ohnishi, Yoshito; Yasutomo, Teruhito; Osako, Yoshifumi

    2005-01-01

    A novel multi-functional vertical high shear kneader has been developed and its performance in wet kneading has previously been reported [Watano et al., Chem. Pharm. Bull., 50(3), 341-345 (2002)]. In this study, scale-up of wet kneading in the novel vertical high shear kneader was conducted. Pharmaceutical excipients composed of lactose, cornstarch and micro-crystalline cellulose were used as powder samples. Kneading operations were conducted under various operating conditions and three different vessel scales. The dried pellets were then prepared by extruding the wet kneaded masses through a dome-type extruder and their drying by a fluidized bed. The physical properties such as strength and disintegration time of the dried pellets were evaluated. It was found that the properties of the dried pellets and their scale-up characteristics were well expressed by an agitation power per unit vessel volume and dimensionless Froude number.

  4. From Project to Program: Tupange's Experience with Scaling Up Family Planning Interventions in Urban Kenya.

    Science.gov (United States)

    Keyonzo, Nelson; Nyachae, Paul; Kagwe, Peter; Kilonzo, Margaret; Mumba, Feddis; Owino, Kenneth; Kichamu, George; Kigen, Bartilol; Fajans, Peter; Ghiron, Laura; Simmons, Ruth

    2015-05-01

    This paper describes how the Urban Reproductive Health Initiative in Kenya, the Tupange Project (2010-2015), successfully applied the ExpandNet approach to sustainably scale up family planning interventions, first in Machakos and Kakamega, and subsequently also in its three core cities, Nairobi, Kisumu and Mombasa. This new focus meant shifting from a "project" to a "program" approach, which required paying attention to government leadership and ownership, limiting external inputs, institutionalizing interventions in existing structures and emphasizing sustainability. The paper also highlights the project's efforts to prepare for the future scale up of Tupange's interventions in other counties to support continuing and improved access to family planning services in the new context of devolution (decentralization) in Kenya. Copyright © 2015. Published by Elsevier Ltd.

  5. Bioprocess engineering for biohythane production from low-grade waste biomass: technical challenges towards scale up.

    Science.gov (United States)

    Liu, Zhidan; Si, Buchun; Li, Jiaming; He, Jianwei; Zhang, Chong; Lu, Yuan; Zhang, Yuanhui; Xing, Xin-Hui

    2017-09-08

    A concept of biohythane production by combining biohydrogen and biomethane together via two-stage anaerobic fermentation (TSAF) has been recently proposed and considered as a promising approach for sustainable hythane generation from waste biomass. The advantage of biohythane over traditional biogas are more environmentally benign, higher energy recovery and shorter fermentation time. However, many of current efforts to convert waste biomass into biohythane are still at the bench scale. The system bioprocess study and scale up for industrial application are indispensable. This paper outlines the general approach of biohythane by comparing with other biological processes. The technical challenges are highlighted towards scale up of biohythane system, including functionalization of biohydrogen-producing reactor, energy efficiency, and bioprocess engineering of TSAF. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Scaling up of HIV-TB collaborative activities: Achievements and challenges in India.

    Science.gov (United States)

    Deshmukh, Rajesh; Shah, Amar; Sachdeva, K S; Sreenivas, A N; Gupta, R S; Khaparde, S D

    2016-01-01

    India has been implementing HIV/TB collaborative activities since 2001 with rapid scale-up of infrastructure across the country during past decade in National AIDS Control Programme and Revised National TB Control Programme. India has shown over 50% reduction in new infections and around 35% reduction in AIDS-related deaths, thereby being one of the success stories globally. Substantial progress in the implementation of collaborative TB/HIV activities has occurred in India and it is marching towards target set out in the Global Plan to Stop TB and endorsed by the UN General Assembly to halve HIV associated TB deaths by 2015. While the successful approaches have led to impressive gains in HIV/TB control in India, there are emerging challenges including newer pockets with rising HIV trends in North India, increasing drug resistance, high mortality among co-infected patients, low HIV testing rates among TB patients in northern and eastern states in India, treatment delays and drop-outs, stigma and discrimination, etc. In spite of these difficulties, established HIV/TB coordination mechanisms at different levels, rapid scale-up of facilities with decentralisation of treatment services, regular joint supervision and monitoring, newer initiatives like use of rapid diagnostics for early diagnosis of TB among people living with HIV, TB notification, etc. have led to success in combating the threat of HIV/TB in India. This article highlights the steps taken by India, one of the largest HIV/TB programmes in world, in scaling up of the joint HIV-TB collaborative activities, the achievements so far and discusses the emerging challenges which could provide important lessons for other countries in scaling up their programmes. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

  7. Chapter 6. Scaling Up Solutions to State, National and Global Levels

    OpenAIRE

    Daniel Kammen; Doug Rotman; Magali Delmas; David Feldman; Mike Mielke; Ramamoorthy Ramesh; Daniel Sperling

    2016-01-01

    Scaling-up solutions require learning and adapting lessons between locations and at different scales. To accomplish this, common metrics are vital to building a shared language. For California, this has meant careful financial, cradle-to-grave life-cycle assessment methods leading to carbon accounting in many avenues of government (via the Low Carbon Fuel Standard or the Cap and Trade program). These methods themselves interact, such as the use of carbon accounting for the resources needed to...

  8. High-Throughput Synthesis, Screening, and Scale-Up of Optimized Conducting Indium Tin Oxides

    OpenAIRE

    Marchand, P; Makwana, N. M.; Tighe, C. J.; Gruar, R. I.; Parkin, I. P.; Carmalt, C. J.; Darr, J. A.

    2016-01-01

    A high-throughput optimization and subsequent scale-up methodology has been used for the synthesis of conductive tin-doped indium oxide (known as ITO) nanoparticles. ITO nanoparticles with up to 12 at % Sn were synthesized using a laboratory scale (15 g/hour by dry mass) continuous hydrothermal synthesis process, and the as-synthesized powders were characterized by powder X-ray diffraction, transmission electron microscopy, energy-dispersive X-ray analysis, and X-ray photoelectron spectroscop...

  9. Development and Scale Up Of a Chemical Process in Pharmaceutical Industry: A Case Study

    OpenAIRE

    Savita Belwal; V. Revanth, K.S.V.V. Dinesh; B. V. Reddy; M. Bhagvanth Rao

    2016-01-01

    Every process has its own significance and one has to study factors which impact to the process and its procedure to be followed. This paper is more concerned of how a process is scaled up from lab scale to pilot plant scale, which is the major step in any industry because moving directly towards manufacturing level consumes time and money. The report introduces about pharmaceutical industry and how it is different from the other industries and provides firsthand experience for al...

  10. Differences in antiretroviral scale up in three South African provinces: the role of implementation management

    Directory of Open Access Journals (Sweden)

    Van Rensburg Dingie

    2010-07-01

    Full Text Available Abstract Background South Africa’s antiretroviral programme is governed by defined national plans, establishing treatment targets and providing funding through ring-fenced conditional grants. However, in terms of the country’s quasi-federal constitution, provincial governments bear the main responsibility for provision of health care, and have a certain amount of autonomy and therefore choice in the way their HIV/AIDS programmes are implemented. Methods The paper is a comparative case study of the early management of ART scale up in three South African provincial governments – Western Cape, Gauteng and Free State – focusing on both operational and strategic dimensions. Drawing on surveys of models of ART care and analyses of the policy process conducted in the three provinces between 2005 and 2007, as well as a considerable body of grey and indexed literature on ART scale up in South Africa, it draws links between implementation processes and variations in provincial ART coverage (low, medium and high achieved in the three provinces. Results While they adopted similar chronic disease care approaches, the provinces differed with respect to political and managerial leadership of the programme, programme design, the balance between central standardisation and local flexibility, the effectiveness of monitoring and evaluation systems, and the nature and extent of external support and programme partnerships. Conclusions This case study points to the importance of sub-national programme processes and the influence of factors other than financing or human resource capacity, in understanding intervention scale up.

  11. Theoretical and Practical Issues That Are Relevant When Scaling Up hMSC Microcarrier Production Processes.

    Science.gov (United States)

    Jossen, Valentin; Schirmer, Cedric; Mostafa Sindi, Dolman; Eibl, Regine; Kraume, Matthias; Pörtner, Ralf; Eibl, Dieter

    2016-01-01

    The potential of human mesenchymal stem cells (hMSCs) for allogeneic cell therapies has created a large amount of interest. However, this presupposes the availability of efficient scale-up procedures. Promising results have been reported for stirred bioreactors that operate with microcarriers. Recent publications focusing on microcarrier-based stirred bioreactors have demonstrated the successful use of Computational Fluid Dynamics (CFD) and suspension criteria (N S1u , N S1) for rapidly scaling up hMSC expansions from mL- to pilot scale. Nevertheless, one obstacle may be the formation of large microcarrier-cell-aggregates, which may result in mass transfer limitations and inhomogeneous distributions of stem cells in the culture broth. The dependence of microcarrier-cell-aggregate formation on impeller speed and shear stress levels was investigated for human adipose derived stromal/stem cells (hASCs) at the spinner scale by recording the Sauter mean diameter (d 32) versus time. Cultivation at the suspension criteria provided d 32 values between 0.2 and 0.7 mm, the highest cell densities (1.25 × 10(6) cells mL(-1) hASCs), and the highest expansion factors (117.0 ± 4.7 on day 7), while maintaining the expression of specific surface markers. Furthermore, suitability of the suspension criterion N S1u was investigated for scaling up microcarrier-based processes in wave-mixed bioreactors for the first time.

  12. Nurse Family Partnership: Comparing Costs per Family in Randomized Trials Versus Scale-Up.

    Science.gov (United States)

    Miller, Ted R; Hendrie, Delia

    2015-12-01

    The literature that addresses cost differences between randomized trials and full-scale replications is quite sparse. This paper examines how costs differed among three randomized trials and six statewide scale-ups of nurse family partnership (NFP) intensive home visitation to low income first-time mothers. A literature review provided data on pertinent trials. At our request, six well-established programs reported their total expenditures. We adjusted the costs to national prices based on mean hourly wages for registered nurses and then inflated them to 2010 dollars. A centralized data system provided utilization. Replications had fewer home visits per family than trials (25 vs. 31, p = .05), lower costs per client ($8860 vs. $12,398, p = .01), and lower costs per visit ($354 vs. $400, p = .30). Sample size limited the significance of these differences. In this type of labor intensive program, costs probably were lower in scale-up than in randomized trials. Key cost drivers were attrition and the stable caseload size possible in an ongoing program. Our estimates reveal a wide variation in cost per visit across six state programs, which suggests that those planning replications should not expect a simple rule to guide cost estimations for scale-ups. Nevertheless, NFP replications probably achieved some economies of scale.

  13. Fermentation scale up for α-arbutin production by Xanthomonas BT-112.

    Science.gov (United States)

    Wei, Meng; Ren, Yi; Liu, Changxia; Liu, Ruican; Zhang, Peng; Wei, Yi; Xu, Tao; Wang, Fang; Tan, Tianwei; Liu, Chunqiao

    2016-09-10

    α-Arbutin is a glycosylated hydroquinone that has an inhibitory function against tyrosinase. The aim of the present study is to develop an efficient and inexpensive method for large-scale production of α-arbutin by using Xanthomonas BT-112 as biocatalyst. To accomplish this goal, various surfactants were tested to enhance the α-arbutin production, and the optimal operational conditions for 30L jar fermenter were scaled up for a production level of 3000L with using a constant volumetric oxygen transfer coefficient (KLa) and the volumetric aeration rate per volume unit (Q/V) as scale-up criteria. Under the optimized conditions, the α-arbutin produced in the presence of 0.4% (w/v) Tween-80 was 124.8% higher than that of the control, and the yield of α-arbutin in 3000L fermenter was 38.2g/L with a molar conversion ratio of 93.7% based on the amount of hydroquinone supplied. This result is comparable to the results from laboratory-scale fermenter. Hence, 100-fold scale-up was successfully achieved. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Differences in antiretroviral scale up in three South African provinces: the role of implementation management.

    Science.gov (United States)

    Schneider, Helen; Coetzee, David; Van Rensburg, Dingie; Gilson, Lucy

    2010-07-02

    South Africa's antiretroviral programme is governed by defined national plans, establishing treatment targets and providing funding through ring-fenced conditional grants. However, in terms of the country's quasi-federal constitution, provincial governments bear the main responsibility for provision of health care, and have a certain amount of autonomy and therefore choice in the way their HIV/AIDS programmes are implemented. The paper is a comparative case study of the early management of ART scale up in three South African provincial governments--Western Cape, Gauteng and Free State--focusing on both operational and strategic dimensions. Drawing on surveys of models of ART care and analyses of the policy process conducted in the three provinces between 2005 and 2007, as well as a considerable body of grey and indexed literature on ART scale up in South Africa, it draws links between implementation processes and variations in provincial ART coverage (low, medium and high) achieved in the three provinces. While they adopted similar chronic disease care approaches, the provinces differed with respect to political and managerial leadership of the programme, programme design, the balance between central standardisation and local flexibility, the effectiveness of monitoring and evaluation systems, and the nature and extent of external support and programme partnerships. This case study points to the importance of sub-national programme processes and the influence of factors other than financing or human resource capacity, in understanding intervention scale up.

  15. Scale-up of nature's tissue weaving algorithms to engineer advanced functional materials.

    Science.gov (United States)

    Ng, Joanna L; Knothe, Lillian E; Whan, Renee M; Knothe, Ulf; Tate, Melissa L Knothe

    2017-01-11

    We are literally the stuff from which our tissue fabrics and their fibers are woven and spun. The arrangement of collagen, elastin and other structural proteins in space and time embodies our tissues and organs with amazing resilience and multifunctional smart properties. For example, the periosteum, a soft tissue sleeve that envelops all nonarticular bony surfaces of the body, comprises an inherently "smart" material that gives hard bones added strength under high impact loads. Yet a paucity of scalable bottom-up approaches stymies the harnessing of smart tissues' biological, mechanical and organizational detail to create advanced functional materials. Here, a novel approach is established to scale up the multidimensional fiber patterns of natural soft tissue weaves for rapid prototyping of advanced functional materials. First second harmonic generation and two-photon excitation microscopy is used to map the microscopic three-dimensional (3D) alignment, composition and distribution of the collagen and elastin fibers of periosteum, the soft tissue sheath bounding all nonarticular bone surfaces in our bodies. Then, using engineering rendering software to scale up this natural tissue fabric, as well as multidimensional weaving algorithms, macroscopic tissue prototypes are created using a computer-controlled jacquard loom. The capacity to prototype scaled up architectures of natural fabrics provides a new avenue to create advanced functional materials.

  16. Scale-up of nature’s tissue weaving algorithms to engineer advanced functional materials

    Science.gov (United States)

    Ng, Joanna L.; Knothe, Lillian E.; Whan, Renee M.; Knothe, Ulf; Tate, Melissa L. Knothe

    2017-01-01

    We are literally the stuff from which our tissue fabrics and their fibers are woven and spun. The arrangement of collagen, elastin and other structural proteins in space and time embodies our tissues and organs with amazing resilience and multifunctional smart properties. For example, the periosteum, a soft tissue sleeve that envelops all nonarticular bony surfaces of the body, comprises an inherently “smart” material that gives hard bones added strength under high impact loads. Yet a paucity of scalable bottom-up approaches stymies the harnessing of smart tissues’ biological, mechanical and organizational detail to create advanced functional materials. Here, a novel approach is established to scale up the multidimensional fiber patterns of natural soft tissue weaves for rapid prototyping of advanced functional materials. First second harmonic generation and two-photon excitation microscopy is used to map the microscopic three-dimensional (3D) alignment, composition and distribution of the collagen and elastin fibers of periosteum, the soft tissue sheath bounding all nonarticular bone surfaces in our bodies. Then, using engineering rendering software to scale up this natural tissue fabric, as well as multidimensional weaving algorithms, macroscopic tissue prototypes are created using a computer-controlled jacquard loom. The capacity to prototype scaled up architectures of natural fabrics provides a new avenue to create advanced functional materials.

  17. Housing and Child Welfare: Emerging Evidence and Implications for Scaling up Services.

    Science.gov (United States)

    Fowler, Patrick J; Farrell, Anne F; Marcal, Katherine E; Chung, Saras; Hovmand, Peter S

    2017-09-01

    Inadequate housing threatens family stability in communities across the United States. This study reviews emerging evidence on housing interventions in the context of scale-up for the child welfare system. In child welfare, scale-up refers to the extent to which fully implemented interventions sustainably alleviate family separations associated with housing instability. It incorporates multiple aspects beyond traditional measures of effectiveness including costs, potential reach, local capacities for implementation, and fit within broader social services. The framework further encompasses everyday circumstances faced by service providers, program administrators, and policymakers who allocate resources under conditions of scarcity and uncertainty. The review of current housing interventions reveals a number of systemic constraints for scale-up in child welfare. Reliance on rental assistance programs limits capacity to address demand, while current practices that target the most vulnerable families may inadvertently diminish effectiveness of the intervention and increase overall demand. Alternative approaches that focus on homelessness prevention and early intervention must be tested in conjunction with community initiatives to increase accessibility of affordable housing. By examining system performance over time, the scalability framework provides an opportunity for more efficient coordination of housing services within and outside of the child welfare system. © Society for Community Research and Action 2017.

  18. The economics of scaling up: cost estimation for HIV/AIDS interventions.

    Science.gov (United States)

    Kumaranayake, Lilani

    2008-07-01

    The scaling up of HIV/AIDS programming has been one of the most extensive undertakings in international public health. Yet decision-makers are encountering significant uncertainties about financing and the need to understand programming costs at different scales of delivery. To review the economic methodologies for examining costs and variation by scale. To summarize and synthesize the current evidence related to the provision of HIV/AIDS interventions and scaling up. We used a review of economic methodologies to generate a conceptual framework for classifying existing data, looking at both short-run and long-run perspectives. A review of the literature was performed using PubMed and available grey literature. Factors facilitating comparison and generalizability are highlighted. There is growing evidence of scale variation among the costs of HIV/AIDS interventions. Scale variation has been found to explain 26-70% of cost variation across locations for similar interventions. Average costs may become larger or smaller as the volume of services expands, depending on the level of coverage and type of intervention. Key constraints to scaling up include infrastructure investments and cost results need to be interpreted in this light. Evidence to date suggests that cost efficiencies associated with scale may reflect different ways of delivering services at higher volumes, including lower quality outputs. There is still, however, an extremely limited economic evidence base and mechanisms to integrate economic analyses into routine programme monitoring are recommended.

  19. Impending extinction crisis of the world's primates: Why primates matter.

    Science.gov (United States)

    Estrada, Alejandro; Garber, Paul A; Rylands, Anthony B; Roos, Christian; Fernandez-Duque, Eduardo; Di Fiore, Anthony; Nekaris, K Anne-Isola; Nijman, Vincent; Heymann, Eckhard W; Lambert, Joanna E; Rovero, Francesco; Barelli, Claudia; Setchell, Joanna M; Gillespie, Thomas R; Mittermeier, Russell A; Arregoitia, Luis Verde; de Guinea, Miguel; Gouveia, Sidney; Dobrovolski, Ricardo; Shanee, Sam; Shanee, Noga; Boyle, Sarah A; Fuentes, Agustin; MacKinnon, Katherine C; Amato, Katherine R; Meyer, Andreas L S; Wich, Serge; Sussman, Robert W; Pan, Ruliang; Kone, Inza; Li, Baoguo

    2017-01-01

    Nonhuman primates, our closest biological relatives, play important roles in the livelihoods, cultures, and religions of many societies and offer unique insights into human evolution, biology, behavior, and the threat of emerging diseases. They are an essential component of tropical biodiversity, contributing to forest regeneration and ecosystem health. Current information shows the existence of 504 species in 79 genera distributed in the Neotropics, mainland Africa, Madagascar, and Asia. Alarmingly, ~60% of primate species are now threatened with extinction and ~75% have declining populations. This situation is the result of escalating anthropogenic pressures on primates and their habitats-mainly global and local market demands, leading to extensive habitat loss through the expansion of industrial agriculture, large-scale cattle ranching, logging, oil and gas drilling, mining, dam building, and the construction of new road networks in primate range regions. Other important drivers are increased bushmeat hunting and the illegal trade of primates as pets and primate body parts, along with emerging threats, such as climate change and anthroponotic diseases. Often, these pressures act in synergy, exacerbating primate population declines. Given that primate range regions overlap extensively with a large, and rapidly growing, human population characterized by high levels of poverty, global attention is needed immediately to reverse the looming risk of primate extinctions and to attend to local human needs in sustainable ways. Raising global scientific and public awareness of the plight of the world's primates and the costs of their loss to ecosystem health and human society is imperative.

  20. Unlike fellows - a review of primate-non-primate associations.

    Science.gov (United States)

    Heymann, Eckhard W; Hsia, Shin S

    2015-02-01

    Throughout many regions of the tropics, non-primate animals - mainly birds and mammals - have been observed to follow primate groups and to exploit dropped food and flushed prey. The anecdotal nature of most of the numerous reports on these primate-non-primate associations (PNPAs) may obscure the biological significance of such associations. We review the existing literature and test predictions concerning the influence of primate traits (body size, activity patterns, dietary strategies, habitat, group size) on the occurrence of PNPAs. Furthermore, we examine the influence of non-primates' dietary strategies on the occurrence of PNPAs, and the distribution of benefits and costs. We detected a strong signal in the geographic distribution of PNPAs, with a larger number of such associations in the Neotropics compared to Africa and Asia. Madagascar lacks PNPAs altogether. Primate body size, activity patterns, habitat and dietary strategies as well as non-primate dietary strategies affect the occurrence of PNPAs, while primate group size did not play a role. Benefits are asymmetrically distributed and mainly accrue to non-primates. They consist of foraging benefits through the consumption of dropped leaves and fruits and flushed prey, and anti-predation benefits through eavesdropping on primate alarm calls and vigilance. Where quantitative information is available, it has been shown that benefits for non-primates can be substantial. The majority of PNPAs can thus be categorized as cases of commensalism, while mutualism is very rare. Our review provides evidence that the ecological function of primates extends beyond their manifold interactions with plants, but may remain underestimated. © 2014 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.

  1. Utah optrode array customization using stereotactic brain atlases and 3-D CAD modeling for optogenetic neocortical interrogation in small rodents and nonhuman primates.

    Science.gov (United States)

    Boutte, Ronald W; Merlin, Sam; Yona, Guy; Griffiths, Brandon; Angelucci, Alessandra; Kahn, Itamar; Shoham, Shy; Blair, Steve

    2017-10-01

    As the optogenetic field expands, the need for precise targeting of neocortical circuits only grows more crucial. This work demonstrates a technique for using Solidworks(®) computer-aided design (CAD) and readily available stereotactic brain atlases to create a three-dimensional (3-D) model of the dorsal region of area visual cortex 4 (V4D) of the macaque monkey (Macaca fascicularis) visual cortex. The 3-D CAD model of the brain was used to customize an [Formula: see text] Utah optrode array (UOA) after it was determined that a high-density ([Formula: see text]) UOA caused extensive damage to marmoset (Callithrix jacchus) primary visual cortex as assessed by electrophysiological recording of spiking activity through a 1.5-mm-diameter through glass via. The [Formula: see text] UOA was customized for optrode length ([Formula: see text]), optrode width ([Formula: see text]), optrode pitch ([Formula: see text]), backplane thickness ([Formula: see text]), and overall form factor ([Formula: see text]). Two [Formula: see text] UOAs were inserted into layer VI of macaque V4D cortices with minimal damage as assessed in fixed tissue cytochrome oxidase staining in nonrecoverable surgeries. Additionally, two [Formula: see text] arrays were implanted in mice (Mus musculus) motor cortices, providing early evidence for long-term tolerability (over 6 months), and for the ability to integrate the UOA with a Holobundle light delivery system toward patterned optogenetic stimulation of cortical networks.

  2. The coevolution of innovation and technical intelligence in primates.

    Science.gov (United States)

    Navarrete, Ana F; Reader, Simon M; Street, Sally E; Whalen, Andrew; Laland, Kevin N

    2016-03-19

    In birds and primates, the frequency of behavioural innovation has been shown to covary with absolute and relative brain size, leading to the suggestion that large brains allow animals to innovate, and/or that selection for innovativeness, together with social learning, may have driven brain enlargement. We examined the relationship between primate brain size and both technical (i.e. tool using) and non-technical innovation, deploying a combination of phylogenetically informed regression and exploratory causal graph analyses. Regression analyses revealed that absolute and relative brain size correlated positively with technical innovation, and exhibited consistently weaker, but still positive, relationships with non-technical innovation. These findings mirror similar results in birds. Our exploratory causal graph analyses suggested that technical innovation shares strong direct relationships with brain size, body size, social learning rate and social group size, whereas non-technical innovation did not exhibit a direct relationship with brain size. Nonetheless, non-technical innovation was linked to brain size indirectly via diet and life-history variables. Our findings support 'technical intelligence' hypotheses in linking technical innovation to encephalization in the restricted set of primate lineages where technical innovation has been reported. Our findings also provide support for a broad co-evolving complex of brain, behaviour, life-history, social and dietary variables, providing secondary support for social and ecological intelligence hypotheses. The ability to gain access to difficult-to-extract, but potentially nutrient-rich, resources through tool use may have conferred on some primates adaptive advantages, leading to selection for brain circuitry that underlies technical proficiency. © 2016 The Author(s).

  3. Radiosynthesis of [{sup 18}F] N-(3-Fluoropropyl)-2-{beta}-Carbomethoxy-3-{beta}-(4-Bromophenyl) Nortropane and the regional brain uptake in non human primate using PET

    Energy Technology Data Exchange (ETDEWEB)

    Chaly, Thomas E-mail: tchaly@nshs.edu; Baldwin, R.M.; Neumeyer, John L.; Hellman, Matthew J.; Dhawan, Vijay; Garg, Pradeep K.; Tamagnan, Gilles; Staley, Julie K.; Al-Tikriti, Mohammed S.; Hou, Yankun; Zoghbi, Sami S.; Gu Xiaohui; Zong, R.; Eidelberg, David

    2004-01-01

    A synthetic procedure for the preparation of [{sup 18}F]FPCBT, an imaging agent for the dopamine transporter (DAT), has been developed. The radiosynthesis was carried out in a two step procedure. Even though the yield was low, we were able to prepare 20 to 30mCi of the product, which was enough for two or three studies. The radiochemical purity was greater than 96%. The in vivo properties of this radiotracer were evaluated using baboon and it showed highest uptake in the striatum. The studies also revealed that the maximum uptake was reached within 7 to 10 minutes post injection. Plasma metabolite analysis indicated that there is only one metabolite and it is less lipophilic than the parent compound. [{sup 18}F]FPCBT displayed good brain uptake and its high target to non target ratio indicate that it is a potential candidate for DAT imaging.

  4. Serotonin transporter occupancy by escitalopram and citalopram in the non-human primate brain: a [(11)C]MADAM PET study.

    Science.gov (United States)

    Finnema, Sjoerd J; Halldin, Christer; Bang-Andersen, Benny; Bundgaard, Christoffer; Farde, Lars

    2015-11-01

    A number of serotonin receptor positron emission tomography (PET) radioligands have been shown to be sensitive to changes in extracellular serotonin concentration, in a generalization of the well-known dopamine competition model. High doses of selective serotonin reuptake inhibitors (SSRIs) decrease serotonin receptor availability in monkey brain, consistent with increased serotonin concentrations. However, two recent studies on healthy human subjects, using a single, lower and clinically relevant SSRI dose, showed increased cortical serotonin receptor radioligand binding, suggesting potential decreases in serotonin concentration in projection regions when initiating treatment. The cross-species differential SSRI effect may be partly explained by serotonin transporter (SERT) occupancy in monkey brain being higher than is clinically relevant. We here determine SERT occupancy after single doses of escitalopram or citalopram by conducting PET measurements with [(11)C]MADAM in monkeys. Relationships between dose, plasma concentration and SERT occupancy were estimated by one-site binding analyses. Binding affinity was expressed as dose (ID50) or plasma concentration (K i) where 50 % SERT occupancy was achieved. Estimated ID50 and K i values were 0.020 mg/kg and 9.6 nmol/L for escitalopram and 0.059 mg/kg and 9.7 nmol/L for citalopram, respectively. Obtained K i values are comparable to values reported in humans. Escitalopram or citalopram doses nearly saturated SERT in previous monkey studies which examined serotonin sensitivity of receptor radioligands. PET-measured cross-species differential effects of SSRI on cortical serotonin concentration may thus be related to SSRI dose. Future monkey studies using SSRI doses inducing clinically relevant SERT occupancy may further illuminate the delayed onset of SSRI therapeutic effects.

  5. Long-term expression and safety of administration of AAVrh.10hCLN2 to the brain of rats and nonhuman primates for the treatment of late infantile neuronal ceroid lipofuscinosis.

    Science.gov (United States)

    Sondhi, Dolan; Johnson, Linda; Purpura, Keith; Monette, Sebastien; Souweidane, Mark M; Kaplitt, Michael G; Kosofsky, Barry; Yohay, Kaleb; Ballon, Douglas; Dyke, Jonathan; Kaminksy, Stephen M; Hackett, Neil R; Crystal, Ronald G

    2012-10-01

    Late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal, lysosomal storage disorder caused by mutations in the CLN2 gene, results in a deficiency of tripeptidyl-peptidase I (TPP-I) activity in neurons. Our prior studies showed that delivery of the human CLN2 cDNA directly to the CNS, using an adeno-associated virus serotype 2 (AAV2) vector, is safe in children with LINCL. As a second-generation strategy, we have demonstrated that AAVrh.10hCLN2, a rhesus-derived AAV vector, mediates wide distribution of TPP-I through the CNS in a murine model. This study tests the hypothesis that direct administration of AAVrh.10hCLN2 to the CNS of rats and nonhuman primates at doses scalable to humans has an acceptable safety profile and mediates significant CLN2 expression in the CNS. A dose of 10(11) genome copies (GC) was administered bilaterally to the striatum of Sprague Dawley rats with sacrifice at 7 and 90 days with no significant impact except for mild vector-related histopathological changes at the site of vector administration. A dose of 1.8×10(12) GC of AAVrh.10hCLN2 was administered to the CNS of 8 African green monkeys. The vector-treated monkeys did not differ from controls in any safety parameter except for mild to moderate white matter edema and inflammation localized to the administration sites of the vector. There were no clinical sequelae to these localized findings. TPP-I activity was >2 SD over background in 31.7±8.1% of brain at 90 days. These findings establish the dose and safety profile for human clinical studies for the treatment of LINCL with AAVrh.10hCLN2.

  6. Ethics of primate use

    OpenAIRE

    Prescott, M J

    2010-01-01

    This article provides an overview of the ethical issues raised by the use of non-human primates (NHPs) in research involving scientific procedures which may cause pain, suffering, distress or lasting harm. It is not an exhaustive review of the literature and views on this subject, and it does not present any conclusions about the moral acceptability or otherwise of NHP research. Rather the aim has been to identify the ethical issues involved and to provide guidance on how th...

  7. Eye-blink behaviors in 71 species of primates.

    Science.gov (United States)

    Tada, Hideoki; Omori, Yasuko; Hirokawa, Kumi; Ohira, Hideki; Tomonaga, Masaki

    2013-01-01

    The present study was performed to investigate the associations between eye-blink behaviors and various other factors in primates. We video-recorded 141 individuals across 71 primate species and analyzed the blink rate, blink duration, and "isolated" blink ratio (i.e., blinks without eye or head movement) in relation to activity rhythms, habitat types, group size, and body size factors. The results showed close relationships between three types of eye-blink measures and body size factors. All of these measures increased as a function of body weight. In addition, diurnal primates showed more blinks than nocturnal species even after controlling for body size factors. The most important findings were the relationships between eye-blink behaviors and social factors, e.g., group size. Among diurnal primates, only the blink rate was significantly correlated even after controlling for body size factors. The blink rate increased as the group size increased. Enlargement of the neocortex is strongly correlated with group size in primate species and considered strong evidence for the social brain hypothesis. Our results suggest that spontaneous eye-blinks have acquired a role in social communication, similar to grooming, to adapt to complex social living during primate evolution.

  8. Eye-Blink Behaviors in 71 Species of Primates

    Science.gov (United States)

    Tada, Hideoki; Omori, Yasuko; Hirokawa, Kumi; Ohira, Hideki; Tomonaga, Masaki

    2013-01-01

    The present study was performed to investigate the associations between eye-blink behaviors and various other factors in primates. We video-recorded 141 individuals across 71 primate species and analyzed the blink rate, blink duration, and “isolated” blink ratio (i.e., blinks without eye or head movement) in relation to activity rhythms, habitat types, group size, and body size factors. The results showed close relationships between three types of eye-blink measures and body size factors. All of these measures increased as a function of body weight. In addition, diurnal primates showed more blinks than nocturnal species even after controlling for body size factors. The most important findings were the relationships between eye-blink behaviors and social factors, e.g., group size. Among diurnal primates, only the blink rate was significantly correlated even after controlling for body size factors. The blink rate increased as the group size increased. Enlargement of the neocortex is strongly correlated with group size in primate species and considered strong evidence for the social brain hypothesis. Our results suggest that spontaneous eye-blinks have acquired a role in social communication, similar to grooming, to adapt to complex social living during primate evolution. PMID:23741522

  9. Scale-up considerations relevant to experimental studies of nuclear waste-package behavior

    Energy Technology Data Exchange (ETDEWEB)

    Coles, D.G.; Peters, R.D.

    1986-04-01

    Results from a study that investigated whether testing large-scale nuclear waste-package assemblages was technically warranted are reported. It was recognized that the majority of the investigations for predicting waste-package performance to date have relied primarily on laboratory-scale experimentation. However, methods for the successful extrapolation of the results from such experiments, both geometrically and over time, to actual repository conditions have not been well defined. Because a well-developed scaling technology exists in the chemical-engineering discipline, it was presupposed that much of this technology could be applicable to the prediction of waste-package performance. A review of existing literature documented numerous examples where a consideration of scaling technology was important. It was concluded that much of the existing scale-up technology is applicable to the prediction of waste-package performance for both size and time extrapolations and that conducting scale-up studies may be technically merited. However, the applicability for investigating the complex chemical interactions needs further development. It was recognized that the complexity of the system, and the long time periods involved, renders a completely theoretical approach to performance prediction almost hopeless. However, a theoretical and experimental study was defined for investigating heat and fluid flow. It was concluded that conducting scale-up modeling and experimentation for waste-package performance predictions is possible using existing technology. A sequential series of scaling studies, both theoretical and experimental, will be required to formulate size and time extrapolations of waste-package performance.

  10. Scaling-up the medical workforce in Timor-Leste: challenges of a great leap forward.

    Science.gov (United States)

    Cabral, Jorge; Dussault, Gilles; Buchan, James; Ferrinho, Paulo

    2013-11-01

    The health services system of Timor-Leste (T-L) will, by 2015, add 800 physicians, most of them trained in Cuba, to the 233 employed by the national health system in 2010-2011. The need for more physicians is not in discussion: poor health indicators, low coverage and utilization of services, and poor quality of services are well documented in T-L. However, the choice of this scaling-up, with a relatively narrow focus on the medical workforce, needs to be assessed for its relevance to the health profile of the country, for its comprehensiveness in terms of other complementary measures needed to make it effective. This article discusses the potential effects of the rapid scaling-up of the medical workforce, and the organizational capacity needed to monitor the process and eventually mitigate any deleterious consequences. The analysis is based on a review of documentation collected on site (T-L) and on interviews with key-informants conducted in 2011. We stress that any workforce scaling-up is not simply a matter of increasing numbers of professionals, but should combine improved training, distribution, working conditions, management and motivation, as a means towards better performing health services' systems. This is a major challenge in a context of limited organizational and managerial capacity, underdeveloped information systems, limited training and research capacity, and dependency on foreign aid and technical assistance. Potential risks are associated with funding the additional costs of recruiting more personnel, associated expenditures on infrastructure, equipment and consumables, the impact on current staff mix, and the expected increased demand for services. We conclude that failing to manage effectively the forthcoming "great leap forward" will have long term effects: formal policies and plans for the balanced development of the health workforce, as well as strengthened institutions are urgently needed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Student and faculty perceptions on the rapid scale-up of medical students in Ethiopia.

    Science.gov (United States)

    Mengistu, Brittney S; Vins, Holly; Kelly, Caitrin M; McGee, Daphne R; Spicer, Jennifer O; Derbew, Miliard; Bekele, Abebe; Mariam, Damen Haile; Del Rio, Carlos; Blumberg, Henry M; Comeau, Dawn L

    2017-01-13

    Ethiopia is a country of over 94 million people that has a severe physician shortage with approximately only 2.5 physicians per 100,000 persons. Recently, the Ethiopian government implemented a "flood and retain" initiative to rapidly increase the quantity of physicians in Ethiopia. Consequently, medical student enrollment at Addis Ababa University (AAU) School of Medicine increased from 100 to approximately 300-400 students per class. This study evaluated the impact of the rapid scale-up in the number of medical students on the quality of medical education at AAU and the impact of the U.S. government-funded Medical Education Partnership Initiative (MEPI) grant awarded to AAU to provide resources to strengthen the quality of medical education at AAU. Qualitative, semi-structured, in-depth interviews were conducted with 22 key informants including faculty members, administrators and medical students at AAU. The audio recordings were transcribed verbatim and interview data were analyzed with thematic analysis. Four key themes emerged from the data. Overall, participants perceived a decrease in the quality of medical education at AAU due to challenges created by the rapid scale-up in the number of medical students. Positive learning environments were described as difficult to achieve due to overcrowding in classrooms and the limited numbers of textbooks. Overall, participants stated that infrastructure improvement is needed to provide adequate medical student training. The medical education initiatives implemented and funded by MEPI have provided significant resources to support the medical student curriculum but additional resources are required to accommodate a large student body. The unprecedented rapid scale-up of medical students has impacted multiple facets of medical education at AAU. It is important to consider the perspectives of students and faculty in order to focus future medical education policies, MEPI programming and the allocation of resources.

  12. Documenting good practices: scaling up the youth friendly health service model in Colombia.

    Science.gov (United States)

    Huaynoca, Silvia; Svanemyr, Joar; Chandra-Mouli, Venkatraman C; Moreno Lopez, Diva Jeaneth

    2015-09-18

    Young people make up for 24.5 % of Latin America's population. Inadequate supply of specific and timely sexual and reproductive health (SRH) services and sexuality education for young people increases their risk of sexual and reproductive ill health. Colombia is one of the few countries in Latin America that has implemented and scaled up specific and differentiated health and SRH services-termed as its Youth Friendly Health Services (YFHS) Model. To provide a systematic description of the crucial factors that facilitated and hindered the scale up process of the YFHS Model in Colombia. A comprehensive literature search on SRH services for young people and national efforts to improve their quality of care in Colombia and neighbouring countries was carried out along with interviews with a selection of key stakeholders. The information gathered was analysed using the World Health Organization-ExpandNet framework (WHO-ExpandNet). In 7 years (2007-2013) of the implementation of the YFHS Model in Colombia more than 800 clinics nationally have been made youth friendly. By 2013, 536 municipalities in 32 departments had YFHS, resulting in coverage of 52 % of municipalities offering YHFS. The analysis using the WHO-ExpandNet framework identified five elements that enabled the scale up process: Clear policies and implementation guidelines on YFHS, clear attributes of the user organization and resource team, establishment and implementation of an inter-sectoral and interagency strategy, identification of and support to stakeholders and advocates of YFHS, and solid monitoring and evaluation. The elements that limited or slowed down the scale up effort were: Insufficient number of health personnel trained in youth health and SRH, a high turnover of health personnel, a decentralized health security system, inadequate supply of financial and human resources, and negative perceptions among community members about providing SRH information and services to young people. Colombia

  13. Scale-up of industrial biodiesel production to 40 m3using a liquid lipase formulation

    DEFF Research Database (Denmark)

    Price, Jason; Nordblad, Mathias; Martel, Hannah H.

    2016-01-01

    In this work, we demonstrate the scale-up from an 80 L fed-batch scale to 40 m3 along with the design of a 4 m3continuous process for enzymatic biodiesel production catalysed by NS-40116 (a liquid formulation of a modified Thermomyces lanuginosus lipase). Based on the analysis of actual pilot plant...... data for the transesterification of used cooking oil and brown grease, we propose a method applying first order integral analysis to fed-batch data based on either the bound glycerol or free fatty acid content in the oil. This method greatly simplifies the modelling process and gives an indication...

  14. Process considerations for the scale-up and implementation of biocatalysis

    DEFF Research Database (Denmark)

    Tufvesson, Pär; Fu, Wenjing; Jensen, Jacob Skibsted

    2010-01-01

    and biocatalysis in particular is a rather young technology. Although significant progress has been made in the implementation of new processes (especially in the pharmaceutical industry) no fixed methods for process design have been established to date. In this paper we present some of the considerations required...... to scale-up a biocatalytic process and some of the recently developed engineering tools available to assist in this procedure. The tools will have a decisive role in helping to identify bottlenecks in the biocatalytic development process and to justify where to put effort and resources....

  15. Bioreactor scale-up and oxygen transfer rate in microbial processes: an overview.

    Science.gov (United States)

    Garcia-Ochoa, Felix; Gomez, Emilio

    2009-01-01

    In aerobic bioprocesses, oxygen is a key substrate; due to its low solubility in broths (aqueous solutions), a continuous supply is needed. The oxygen transfer rate (OTR) must be known, and if possible predicted to achieve an optimum design operation and scale-up of bioreactors. Many studies have been conducted to enhance the efficiency of oxygen transfer. The dissolved oxygen concentration in a suspension of aerobic microorganisms depends on the rate of oxygen transfer from the gas phase to the liquid, on the rate at which oxygen is transported into the cells (where it is consumed), and on the oxygen uptake rate (OUR) by the microorganism for growth, maintenance and production. The gas-liquid mass transfer in a bioprocess is strongly influenced by the hydrodynamic conditions in the bioreactors. These conditions are known to be a function of energy dissipation that depends on the operational conditions, the physicochemical properties of the culture, the geometrical parameters of the bioreactor and also on the presence of oxygen consuming cells. Stirred tank and bubble column (of various types) bioreactors are widely used in a large variety of bioprocesses (such as aerobic fermentation and biological wastewater treatments, among others). Stirred tanks bioreactors provide high values of mass and heat transfer rates and excellent mixing. In these systems, a high number of variables affect the mass transfer and mixing, but the most important among them are stirrer speed, type and number of stirrers and gas flow rate used. In bubble columns and airlifts, the low-shear environment compared to the stirred tanks has enabled successful cultivation of shear sensitive and filamentous cells. Oxygen transfer is often the rate-limiting step in the aerobic bioprocess due to the low solubility of oxygen in the medium. The correct measurement and/or prediction of the volumetric mass transfer coefficient, (k(L)a), is a crucial step in the design, operation and scale-up of

  16. An integrated health sector response to violence against women in Malaysia: lessons for supporting scale up

    Directory of Open Access Journals (Sweden)

    Colombini Manuela

    2012-07-01

    Full Text Available Abstract Background Malaysia has been at the forefront of the development and scale up of One-Stop Crisis Centres (OSCC - an integrated health sector model that provides comprehensive care to women and children experiencing physical, emotional and sexual abuse. This study explored the strengths and challenges faced during the scaling up of the OSCC model to two States in Malaysia in order to identify lessons for supporting successful scale-up. Methods In-depth interviews were conducted with health care providers, policy makers and key informants in 7 hospital facilities. This was complemented by a document analysis of hospital records and protocols. Data were coded and analysed using NVivo 7. Results The implementation of the OSCC model differed between hospital settings, with practise being influenced by organisational systems and constraints. Health providers generally tried to offer care to abused women, but they are not fully supported within their facility due to lack of training, time constraints, limited allocated budget, or lack of referral system to external support services. Non-specialised hospitals in both States struggled with a scarcity of specialised staff and limited referral options for abused women. Despite these challenges, even in more resource-constrained settings staff who took the initiative found it was possible to adapt to provide some level of OSCC services, such as referring women to local NGOs or community support groups, or training nurses to offer basic counselling. Conclusions The national implementation of OSCC provides a potentially important source of support for women experiencing violence. Our findings confirm that pilot interventions for health sector responses to gender based violence can be scaled up only when there is a sound health infrastructure in place – in other words a supportive health system. Furthermore, the successful replication of the OSCC model in other similar settings requires that the

  17. Scaling Up Early Infant Male Circumcision: Lessons From the Kingdom of Swaziland.

    Science.gov (United States)

    Fitzgerald, Laura; Benzerga, Wendy; Mirira, Munamato; Adamu, Tigistu; Shissler, Tracey; Bitchong, Raymond; Malaza, Mandla; Mamba, Makhosini; Mangara, Paul; Curran, Kelly; Khumalo, Thembisile; Mlambo, Phumzile; Njeuhmeli, Emmanuel; Maziya, Vusi

    2016-07-01

    The government of the Kingdom of Swaziland recognizes that it must urgently scale up HIV prevention interventions, such as voluntary medical male circumcision (VMMC). Swaziland has adopted a 2-phase approach to male circumcision scale-up. The catch-up phase prioritizes VMMC services for adolescents and adults, while the sustainability phase involves the establishment of early infant male circumcision (EIMC). Swaziland does not have a modern-day tradition of circumcision, and the VMMC program has met with client demand challenges. However, since the launch of the EIMC program in 2010, Swaziland now leads the Eastern and Southern Africa region in the scale-up of EIMC. Here we review Swaziland's program and its successes and challenges. From February to May 2014, we collected data while preparing Swaziland's "Male Circumcision Strategic and Operational Plan for HIV Prevention 2014-2018." We conducted structured stakeholder focus group discussions and in-depth interviews, and we collected EIMC service delivery data from an implementing partner responsible for VMMC and EIMC service delivery. Data were summarized in consolidated narratives. Between 2010 and 2014, trained providers performed more than 5,000 EIMCs in 11 health care facilities in Swaziland, and they reported no moderate or severe adverse events. According to a broad group of EIMC program stakeholders, an EIMC program needs robust support from facility, regional, and national leadership, both within and outside of HIV prevention coordination bodies, to promote institutionalization and ownership. Providers and health care managers in 3 of Swaziland's 4 regional hospitals suggest that when EIMC is introduced into reproductive, maternal, newborn, and child health platforms, dedicated staff attention can help ensure that EIMC is performed amid competing priorities. Creating informed demand from communities also supports EIMC as a service delivery priority. Formative research shows that EIMC programs should

  18. Studying Scale-Up and Spread as Social Practice: Theoretical Introduction and Empirical Case Study.

    Science.gov (United States)

    Shaw, James; Shaw, Sara; Wherton, Joseph; Hughes, Gemma; Greenhalgh, Trisha

    2017-07-07

    Health and care technologies often succeed on a small scale but fail to achieve widespread use (scale-up) or become routine practice in other settings (spread). One reason for this is under-theorization of the process of scale-up and spread, for which a potentially fruitful theoretical approach is to consider the adoption and use of technologies as social practices. This study aimed to use an in-depth case study of assisted living to explore the feasibility and usefulness of a social practice approach to explaining the scale-up of an assisted-living technology across a local system of health and social care. This was an individual case study of the implementation of a Global Positioning System (GPS) "geo-fence" for a person living with dementia, nested in a much wider program of ethnographic research and organizational case study of technology implementation across health and social care (Studies in Co-creating Assisted Living Solutions [SCALS] in the United Kingdom). A layered sociological analysis included micro-level data on the index case, meso-level data on the organization, and macro-level data on the wider social, technological, economic, and political context. Data (interviews, ethnographic notes, and documents) were analyzed and synthesized using structuration theory. A social practice lens enabled the uptake of the GPS technology to be studied in the context of what human actors found salient, meaningful, ethical, legal, materially possible, and professionally or culturally appropriate in particular social situations. Data extracts were used to illustrate three exemplar findings. First, professional practice is (and probably always will be) oriented not to "implementing technologies" but to providing excellent, ethical care to sick and vulnerable individuals. Second, in order to "work," health and care technologies rely heavily on human relationships and situated knowledge. Third, such technologies do not just need to be adopted by individuals; they need

  19. Advanced modeling to accelerate the scale up of carbon capture technologies

    Energy Technology Data Exchange (ETDEWEB)

    Miller, David C.; Sun, XIN; Storlie, Curtis B.; Bhattacharyya, Debangsu

    2015-06-01

    In order to help meet the goals of the DOE carbon capture program, the Carbon Capture Simulation Initiative (CCSI) was launched in early 2011 to develop, demonstrate, and deploy advanced computational tools and validated multi-scale models to reduce the time required to develop and scale-up new carbon capture technologies. This article focuses on essential elements related to the development and validation of multi-scale models in order to help minimize risk and maximize learning as new technologies progress from pilot to demonstration scale.

  20. An integrated health sector response to violence against women in Malaysia: lessons for supporting scale up.

    Science.gov (United States)

    Colombini, Manuela; Mayhew, Susannah H; Ali, Siti Hawa; Shuib, Rashidah; Watts, Charlotte

    2012-07-24

    Malaysia has been at the forefront of the development and scale up of One-Stop Crisis Centres (OSCC) - an integrated health sector model that provides comprehensive care to women and children experiencing physical, emotional and sexual abuse. This study explored the strengths and challenges faced during the scaling up of the OSCC model to two States in Malaysia in order to identify lessons for supporting successful scale-up. In-depth interviews were conducted with health care providers, policy makers and key informants in 7 hospital facilities. This was complemented by a document analysis of hospital records and protocols. Data were coded and analysed using NVivo 7. The implementation of the OSCC model differed between hospital settings, with practise being influenced by organisational systems and constraints. Health providers generally tried to offer care to abused women, but they are not fully supported within their facility due to lack of training, time constraints, limited allocated budget, or lack of referral system to external support services. Non-specialised hospitals in both States struggled with a scarcity of specialised staff and limited referral options for abused women. Despite these challenges, even in more resource-constrained settings staff who took the initiative found it was possible to adapt to provide some level of OSCC services, such as referring women to local NGOs or community support groups, or training nurses to offer basic counselling. The national implementation of OSCC provides a potentially important source of support for women experiencing violence. Our findings confirm that pilot interventions for health sector responses to gender based violence can be scaled up only when there is a sound health infrastructure in place - in other words a supportive health system. Furthermore, the successful replication of the OSCC model in other similar settings requires that the model - and the system supporting it - needs to be flexible enough to

  1. Mammalian Brains Are Made of These: A Dataset of the Numbers and Densities of Neuronal and Nonneuronal Cells in the Brain of Glires, Primates, Scandentia, Eulipotyphlans, Afrotherians and Artiodactyls, and Their Relationship with Body Mass.

    Science.gov (United States)

    Herculano-Houzel, Suzana; Catania, Kenneth; Manger, Paul R; Kaas, Jon H

    2015-01-01

    Comparative studies amongst extant species are one of the pillars of evolutionary neurobiology. In the 20th century, most comparative studies remained restricted to analyses of brain structure volume and surface areas, besides estimates of neuronal density largely limited to the cerebral cortex. Over the last 10 years, we have amassed data on the numbers of neurons and other cells that compose the entirety of the brain (subdivided into cerebral cortex, cerebellum, and rest of brain) of 39 mammalian species spread over 6 clades, as well as their densities. Here we provide that entire dataset in a format that is readily useful to researchers of any area of interest in the hope that it will foster the advancement of evolutionary and comparative studies well beyond the scope of neuroscience itself. We also reexamine the relationship between numbers of neurons, neuronal densities and body mass, and find that in the rest of brain, but not in the cerebral cortex or cerebellum, there is a single scaling rule that applies to average neuronal cell size, which increases with the linear dimension of the body, even though there is no single scaling rule that relates the number of neurons in the rest of brain to body mass. Thus, larger bodies do not uniformly come with more neurons--but they do fairly uniformly come with larger neurons in the rest of brain, which contains a number of structures directly connected to sources or targets in the body. © 2015 S. Karger AG, Basel.

  2. Safer operating conditions and optimal scaling-up process for cyclohexanone peroxide reaction

    Energy Technology Data Exchange (ETDEWEB)

    Zang, Na [Department of Fire Protection Engineering, Chinese People' s Armed Police Force Academy, Langfang 065000, Hebei (China); Jiangsu Key Laboratory of Urban and Industrial Safety, Nanjing University of Technology, Nanjing 211800, Jiangsu (China); Qian, Xin-Ming, E-mail: qsemon@bit.edu.cn [State Key Laboratory of Explosion Science and Technology, Beijing Institute of Technology, Beijing 100081 (China); Liu, Zhen-Yi [State Key Laboratory of Explosion Science and Technology, Beijing Institute of Technology, Beijing 100081 (China); Shu, Chi-Min [Process Safety and Disaster Prevention Laboratory, Department of Safety, Health, and Environmental Engineering, National Yunlin University of Science and Technology, Douliou, Yunlin 64002, Taiwan, ROC (China)

    2015-10-20

    Highlights: • Thermal hazard of cyclohexanone peroxide reaction was measured by experimental techniques. • Levenberg–Marquardt algorithm was adopted to evaluate kinetic parameters. • Safer operating conditions at laboratory scale were acquired by BDs and TDs. • The verified safer operating conditions were used to obtain the optimal scale-up parameters applied in industrial plants. - Abstract: The cyclohexanone peroxide reaction process, one of the eighteen hazardous chemical processes identified in China, is performed in indirectly cooled semibatch reactors. The peroxide reaction is added to a mixture of hydrogen peroxide and nitric acid, which form heterogeneous liquid–liquid systems. A simple and general procedure for building boundary and temperature diagrams of peroxide process is given here to account for the overall kinetic expressions. Such a procedure has been validated by comparison with experimental data. Thermally safer operating parameters were obtained at laboratory scale, and the scaled-up procedure was performed to give the minimum dosing time in an industrial plant, which is in favor of maximizing industrial reactor productivity. The results are of great significance for governing the peroxide reaction process apart from the thermal runaway region. It also greatly aids in determining optimization on operating parameters in industrial plants.

  3. Semantic Representation and Scale-Up of Integrated Air Traffic Management Data

    Science.gov (United States)

    Keller, Richard M.; Ranjan, Shubha; Wei, Mie; Eshow, Michelle

    2016-01-01

    Each day, the global air transportation industry generates a vast amount of heterogeneous data from air carriers, air traffic control providers, and secondary aviation entities handling baggage, ticketing, catering, fuel delivery, and other services. Generally, these data are stored in isolated data systems, separated from each other by significant political, regulatory, economic, and technological divides. These realities aside, integrating aviation data into a single, queryable, big data store could enable insights leading to major efficiency, safety, and cost advantages. In this paper, we describe an implemented system for combining heterogeneous air traffic management data using semantic integration techniques. The system transforms data from its original disparate source formats into a unified semantic representation within an ontology-based triple store. Our initial prototype stores only a small sliver of air traffic data covering one day of operations at a major airport. The paper also describes our analysis of difficulties ahead as we prepare to scale up data storage to accommodate successively larger quantities of data -- eventually covering all US commercial domestic flights over an extended multi-year timeframe. We review several approaches to mitigating scale-up related query performance concerns.

  4. Biological hydrogen production by dark fermentation: challenges and prospects towards scaled-up production.

    Science.gov (United States)

    RenNanqi; GuoWanqian; LiuBingfeng; CaoGuangli; DingJie

    2011-06-01

    Among different technologies of hydrogen production, bio-hydrogen production exhibits perhaps the greatest potential to replace fossil fuels. Based on recent research on dark fermentative hydrogen production, this article reviews the following aspects towards scaled-up application of this technology: bioreactor development and parameter optimization, process modeling and simulation, exploitation of cheaper raw materials and combining dark-fermentation with photo-fermentation. Bioreactors are necessary for dark-fermentation hydrogen production, so the design of reactor type and optimization of parameters are essential. Process modeling and simulation can help engineers design and optimize large-scale systems and operations. Use of cheaper raw materials will surely accelerate the pace of scaled-up production of biological hydrogen. And finally, combining dark-fermentation with photo-fermentation holds considerable promise, and has successfully achieved maximum overall hydrogen yield from a single substrate. Future development of bio-hydrogen production will also be discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Disaster risk reduction education in Indonesia: challenges and recommendations for scaling up

    Science.gov (United States)

    Amri, Avianto; Bird, Deanne K.; Ronan, Kevin; Haynes, Katharine; Towers, Briony

    2017-04-01

    This article investigates the implementation of disaster risk reduction education for children in Indonesia. In the last decade, education programmes related to this subject have been promoted as capable of reducing disaster losses and increasing resilience, based on several studies that have identified positive outcomes. Therefore, it is critical to evaluate and address any potential challenges that might impede their success. The article uses a case study in Jakarta, a rapidly growing megacity that is highly prone to disasters and natural hazards, especially floods and fires, to explore the scaling up and sustainability of disaster risk reduction in Indonesian schools. Based on previous studies, a new approach was developed for evaluating the implementation of education programmes related to these subjects. This study captured the perspectives of children, school personnel, and non-governmental organisations on the challenges of scaling up the implementation of disaster risk reduction education in schools. The study revealed seven key issues and suggests several policy recommendations to move forward. These key issues may also be apparent in many other developing and developed countries, and the suggested recommendations may well be applicable beyond Indonesia.

  6. Increasing power generation for scaling up single-chamber air cathode microbial fuel cells

    KAUST Repository

    Cheng, Shaoan

    2011-03-01

    Scaling up microbial fuel cells (MFCs) requires a better understanding the importance of the different factors such as electrode surface area and reactor geometry relative to solution conditions such as conductivity and substrate concentration. It is shown here that the substrate concentration has significant effect on anode but not cathode performance, while the solution conductivity has a significant effect on the cathode but not the anode. The cathode surface area is always important for increasing power. Doubling the cathode size can increase power by 62% with domestic wastewater, but doubling the anode size increases power by 12%. Volumetric power density was shown to be a linear function of cathode specific surface area (ratio of cathode surface area to reactor volume), but the impact of cathode size on power generation depended on the substrate strength (COD) and conductivity. These results demonstrate the cathode specific surface area is the most critical factor for scaling-up MFCs to obtain high power densities. © 2010 Elsevier Ltd.

  7. Scaling-up the production of thermostable lipolytic enzymes from Thermus aquaticus YT1.

    Science.gov (United States)

    López, Elena; Domínguez, Begoña; Deive, Francisco J; Sanromán, M Ángeles; Longo, María A

    2012-08-01

    The lipolytic enzymes synthesized by Thermusaquaticus YT1 present extremely interesting properties of thermostability (more than 70% of activity after 12 days at 80°C and a half-life time of 1 h at 95°C), which point out the interest of proposing efficient strategies to successfully tackle the scale-up of the production process. In this study,viable scaling-up of the production process was implemented,and relevant aspects affecting the enzyme synthesis, such as the mineral composition of the culture medium, the aeration and the agitation have been evaluated.A strategy combining the modification of the culture medium and the aeration degree was also approached by adding perfluorocarbons, compounds which improve the availability of oxygen in the culture medium. An opposite response of biomass and lipolytic activity to the aeration conditions was found between scales (about 600 U L(-1) at high aeration levels in flask vs. 150 U L(-1) at high aeration rates in reactor), which further demonstrates the important role of the hydrodynamic conditions on the suitable development of the biological process. In all cases, the cultures were kinetically characterized and the Luedeking and Piret model turned out to be a valuable tool to conclude that the produced lipolytic enzyme is a growth-associated metabolite, no matter the medium and the scale.

  8. Scaling up: A guide to high throughput genomic approaches for biodiversity analysis.

    Science.gov (United States)

    Porter, Teresita M; Hajibabaei, Mehrdad

    2018-01-02

    The purpose of this review is to present the most common and emerging DNA-based methods used to generate data for biodiversity and biomonitoring studies. Since environmental assessment and monitoring programs may require biodiversity information at multiple levels, we pay particular attention to the DNA metabarcoding method and discuss a number of bioinformatic tools and considerations for producing DNA-based indicators using operational taxonomic units (OTUs), taxa at a variety of ranks, and community composition. By developing the capacity to harness the advantages provided by the newest technologies, investigators can 'scale-up' by increasing the number of samples and replicates processed, the frequency of sampling over time and space, and even the depth of sampling such as by sequencing more reads per sample or more markers per sample. The ability to scale-up is made possible by the reduced hands-on time and cost per sample provided by the newest kits, platforms, and software tools. Results gleaned from broad-scale monitoring will provide an opportunity to address key scientific questions linked to biodiversity and its dynamics across time and space as well as being more relevant for policy makers, enabling science-based decision making, and provide a greater socio-economic impact. Since genomic approaches are continually evolving, we provide this guide to methods used in biodiversity genomics. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. Biohydrogen production from microalgal biomass: energy requirement, CO2 emissions and scale-up scenarios.

    Science.gov (United States)

    Ferreira, Ana F; Ortigueira, Joana; Alves, Luís; Gouveia, Luísa; Moura, Patrícia; Silva, Carla

    2013-09-01

    This paper presents a life cycle inventory of biohydrogen production by Clostridium butyricum through the fermentation of the whole Scenedesmus obliquus biomass. The main purpose of this work was to determine the energy consumption and CO2 emissions during the production of hydrogen. This was accomplished through the fermentation of the microalgal biomass cultivated in an outdoor raceway pond and the preparation of the inoculum and culture media. The scale-up scenarios are discussed aiming for a potential application to a fuel cell hybrid taxi fleet. The H2 yield obtained was 7.3 g H2/kg of S. obliquus dried biomass. The results show that the production of biohydrogen required 71-100 MJ/MJ(H2) and emitted about 5-6 kg CO2/MJ(H2). Other studies and production technologies were taken into account to discuss an eventual process scale-up. Increased production rates of microalgal biomass and biohydrogen are necessary for bioH2 to become competitive with conventional production pathways. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Microbial electrolysis cell scale-up for combined wastewater treatment and hydrogen production.

    Science.gov (United States)

    Gil-Carrera, L; Escapa, A; Mehta, P; Santoyo, G; Guiot, S R; Morán, A; Tartakovsky, B

    2013-02-01

    This study demonstrates microbial electrolysis cell (MEC) scale-up from a 50mL to a 10L cell. Initially, a 50mL membraneless MEC with a gas diffusion cathode was operated on synthetic wastewater at different organic loads. It was concluded that process scale-up might be best accomplished using a "reactor-in-series" concept. Consequently, 855mL and 10L MECs were built and operated. By optimizing the hydraulic retention time (HRT) of the 855mL MEC and individually controlling the applied voltages of three anodic compartments with a real-time optimization algorithm, a COD removal of 5.7g L(R)(-1)d(-1) and a hydrogen production of 1.0-2.6L L(R)(-1)d(-1) was achieved. Furthermore, a two MECs in series 10L setup was constructed and operated on municipal wastewater. This test showed a COD removal rate of 0.5g L(R)(-1)d(-1), a removal efficiency of 60-76%, and an energy consumption of 0.9Whperg of COD removed. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  11. The design and scale-up of spray dried particle delivery systems.

    Science.gov (United States)

    Al-Khattawi, Ali; Bayly, Andrew; Phillips, Andrew; Wilson, David

    2018-01-01

    The rising demand for pharmaceutical particles with tailored physicochemical properties has opened new markets for spray drying especially for solubility enhancement, improving inhalation medicines and stabilization of biopharmaceuticals. Despite this, the spray drying literature is scattered and often does not address the principles underpinning robust development of pharmaceuticals. It is therefore necessary to present clearer picture of the field and highlight the factors influencing particle design and scale-up. Areas covered: The review presents a systematic analysis of the trends in development of particle delivery systems using spray drying. This is followed by exploring the mechanisms governing particle formation in the process stages. Particle design factors including those of equipment configurations and feed/process attributes were highlighted. Finally, the review summarises the current industrial approaches for upscaling pharmaceutical spray drying. Expert opinion: Spray drying provides the ability to design particles of the desired functionality. This greatly benefits the pharmaceutical sector especially as product specifications are becoming more encompassing and exacting. One of the biggest barriers to product translation remains one of scale-up/scale-down. A shift from trial and error approaches to model-based particle design helps to enhance control over product properties. To this end, process innovations and advanced manufacturing technologies are particularly welcomed.

  12. [Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (I)].

    Science.gov (United States)

    Toledano, A; Alvarez, M I; López-Rodríguez, A B; Toledano-Díaz, A; Fernández-Verdecia, C I

    2012-01-01

    Many publications consider that Alzheimer's disease (AD) is exclusive to the human species, and that no other animal species suffers from the disease. However, various studies have shown that some species can present with some of the defining characteristics of the human disease, including both neuropathological changes and cognitive-behavioural symptoms. In this work, the results published (PubMed) on senile brain changes in non-human primates of different degrees of evolution, are reviewed. The neuropathological changes associated with the accumulation of amyloid or highly phosphorylated tau protein are rare outside the primate order, but in all the sub-orders, families, genera and species of non-human primates that have been studied, some senile individuals have shown amyloid accumulation in the brain. In fact, in some species the presence of these deposits in senility is constant. Changes related to the accumulation of tau protein are always of very little significance, and have been detected only in some non-human primate species, both little evolved and highly evolved. In different species of non-human primates, some types of cognitive-behavioural changes are more common in some senile individuals when compared with both normal adult individuals and other senile individuals of the species. The importance of determining the longevity of the species in different habitats (natural habitats, new habitats, semi-captivity, captivity) is stressed in these studies. Morphological, histochemical and cognitive-behavioural features similar to those observed in elderly humans are present in senile non-human primates. Moreover, other characteristics seen in non-human primates could be indicative of a pathological «Alzheimer type» ageing. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  13. Array-based assay detects genome-wide 5-mC and 5-hmC in the brains of humans, non-human primates, and mice.

    Science.gov (United States)

    Chopra, Pankaj; Papale, Ligia A; White, Andrew T J; Hatch, Andrea; Brown, Ryan M; Garthwaite, Mark A; Roseboom, Patrick H; Golos, Thaddeus G; Warren, Stephen T; Alisch, Reid S

    2014-02-13

    Methylation on the fifth position of cytosine (5-mC) is an essential epigenetic mark that is linked to both normal neurodevelopment and neurological diseases. The recent identification of another modified form of cytosine, 5-hydroxymethylcytosine (5-hmC), in both stem cells and post-mitotic neurons, raises new questions as to the role of this base in mediating epigenetic effects. Genomic studies of these marks using model systems are limited, particularly with array-based tools, because the standard method of detecting DNA methylation cannot distinguish between 5-mC and 5-hmC and most methods have been developed to only survey the human genome. We show that non-human data generated using the optimization of a widely used human DNA methylation array, designed only to detect 5-mC, reproducibly distinguishes tissue types within and between chimpanzee, rhesus, and mouse, with correlations near the human DNA level (R(2) > 0.99). Genome-wide methylation analysis, using this approach, reveals 6,102 differentially methylated loci between rhesus placental and fetal tissues with pathways analysis significantly overrepresented for developmental processes. Restricting the analysis to oncogenes and tumor suppressor genes finds 76 differentially methylated loci, suggesting that rhesus placental tissue carries a cancer epigenetic signature. Similarly, adapting the assay to detect 5-hmC finds highly reproducible 5-hmC levels within human, rhesus, and mouse brain tissue that is species-specific with a hierarchical abundance among the three species (human > rhesus > mouse). Annotation of 5-hmC with respect to gene structure reveals a significant prevalence in the 3'UTR and an association with chromatin-related ontological terms, suggesting an epigenetic feedback loop mechanism for 5-hmC. Together, these data show that this array-based methylation assay is generalizable to all mammals for the detection of both 5-mC and 5-hmC, greatly improving the utility of mammalian model systems

  14. Visual cortical areas of the mouse: comparison of parcellation and network structure with primates

    Directory of Open Access Journals (Sweden)

    Marie-Eve eLaramée

    2015-01-01

    Full Text Available Brains have evolved to optimize sensory processing. In primates, complex cognitive tasks must be executed and evolution led to the development of large brains with many cortical areas. Rodents do not accomplish cognitive tasks of the same level of complexity as primates and remain with small brains both in relative and absolute terms. But is a small brain necessarily a simple brain? In this review, several aspects of the visual cortical networks have been compared between rodents and primates. The visual system has been used as a model to evaluate the level of complexity of the cortical circuits at the anatomical and functional levels. The evolutionary constraints are first presented in order to appreciate the rules for the development of the brain and its underlying circuits. The organization of sensory pathways, with their parallel and cross-modal circuits, is also examined. Other features of brain networks, often considered as imposing constraints on the development of underlying circuitry, are also discussed and their effect on the complexity of the mouse and primate brain are inspected. In this review, we discuss the common features of cortical circuits in mice and primates and see how these can be useful in understanding visual processing in these animals.

  15. Visual cortical areas of the mouse: comparison of parcellation and network structure with primates.

    Science.gov (United States)

    Laramée, Marie-Eve; Boire, Denis

    2014-01-01

    Brains have evolved to optimize sensory processing. In primates, complex cognitive tasks must be executed and evolution led to the development of large brains with many cortical areas. Rodents do not accomplish cognitive tasks of the same level of complexity as primates and remain with small brains both in relative and absolute terms. But is a small brain necessarily a simple brain? In this review, several aspects of the visual cortical networks have been compared between rodents and primates. The visual system has been used as a model to evaluate the level of complexity of the cortical circuits at the anatomical and functional levels. The evolutionary constraints are first presented in order to appreciate the rules for the development of the brain and its underlying circuits. The organization of sensory pathways, with their parallel and cross-modal circuits, is also examined. Other features of brain networks, often considered as imposing constraints on the development of underlying circuitry, are also discussed and their effect on the complexity of the mouse and primate brain are inspected. In this review, we discuss the common features of cortical circuits in mice and primates and see how these can be useful in understanding visual processing in these animals.

  16. Scaling up watershed model parameters--Flow and load simulations of the Edisto River Basin

    Science.gov (United States)

    Feaster, Toby D.; Benedict, Stephen T.; Clark, Jimmy M.; Bradley, Paul M.; Conrads, Paul

    2014-01-01

    The Edisto River is the longest and largest river system completely contained in South Carolina and is one of the longest free flowing blackwater rivers in the United States. The Edisto River basin also has fish-tissue mercury concentrations that are some of the highest recorded in the United States. As part of an effort by the U.S. Geological Survey to expand the understanding of relations among hydrologic, geochemical, and ecological processes that affect fish-tissue mercury concentrations within the Edisto River basin, analyses and simulations of the hydrology of the Edisto River basin were made with the topography-based hydrological model (TOPMODEL). The potential for scaling up a previous application of TOPMODEL for the McTier Creek watershed, which is a small headwater catchment to the Edisto River basin, was assessed. Scaling up was done in a step-wise process beginning with applying the calibration parameters, meteorological data, and topographic wetness index data from the McTier Creek TOPMODEL to the Edisto River TOPMODEL. Additional changes were made with subsequent simulations culminating in the best simulation, which included meteorological and topographic wetness index data from the Edisto River basin and updated calibration parameters for some of the TOPMODEL calibration parameters. Comparison of goodness-of-fit statistics between measured and simulated daily mean streamflow for the two models showed that with calibration, the Edisto River TOPMODEL produced slightly better results than the McTier Creek model, despite the significant difference in the drainage-area size at the outlet locations for the two models (30.7 and 2,725 square miles, respectively). Along with the TOPMODEL hydrologic simulations, a visualization tool (the Edisto River Data Viewer) was developed to help assess trends and influencing variables in the stream ecosystem. Incorporated into the visualization tool were the water-quality load models TOPLOAD, TOPLOAD-H, and LOADEST

  17. Health system governance to support scale up of mental health care in Ethiopia: a qualitative study.

    Science.gov (United States)

    Hanlon, Charlotte; Eshetu, Tigist; Alemayehu, Daniel; Fekadu, Abebaw; Semrau, Maya; Thornicroft, Graham; Kigozi, Fred; Marais, Debra Leigh; Petersen, Inge; Alem, Atalay

    2017-01-01

    Ethiopia is embarking upon a ground-breaking plan to address the high levels of unmet need for mental health care by scaling up mental health care integrated within primary care. Health system governance is expected to impact critically upon the success or otherwise of this important initiative. The objective of the study was to explore the barriers, facilitators and potential strategies to promote good health system governance in relation to scale-up of mental health care in Ethiopia. A qualitative study was conducted using in-depth interviews. Key informants were selected purposively from national and regional level policy-makers, planners and service developers (n = 7) and district health office administrators and facility heads (n = 10) from a district in southern Ethiopia where a demonstration project to integrate mental health into primary care is underway. Topic guide development and analysis of transcripts were guided by an established framework for assessing health system governance, adapted for the Ethiopian context. From the perspective of respondents, particular strengths of health system governance in Ethiopia included the presence of high level government support, the existence of a National Mental Health Strategy and the focus on integration of mental health care into primary care to improve the responsiveness of the health system. However, both national and district level respondents expressed concerns about low baseline awareness about mental health care planning, the presence of stigmatising attitudes, the level of transparency about planning decisions, limited leadership for mental health, lack of co-ordination of mental health planning, unreliable supplies of medication, inadequate health management information system indicators for monitoring implementation, unsustainable models for specialist mental health professional involvement in supervision and mentoring of primary care staff, lack of community mobilisation for mental health and low

  18. Scaling up cervical cancer screening in the midst of human papillomavirus vaccination advocacy in Thailand

    Directory of Open Access Journals (Sweden)

    Teerawattananon Yot

    2010-07-01

    Full Text Available Abstract Background Screening tests for cervical cancer are effective in reducing the disease burden. In Thailand, a Pap smear program has been implemented throughout the country for 40 years. In 2008 the Ministry of Public Health (MoPH unexpectedly decided to scale up the coverage of free cervical cancer screening services, to meet an ambitious target. This study analyzes the processes and factors that drove this policy innovation in the area of cervical cancer control in Thailand. Methods In-depth interviews with key policy actors and review of relevant documents were conducted in 2009. Data analysis was guided by a framework, developed on public policy models and existing literature on scaling-up health care interventions. Results Between 2006 and 2008 international organizations and the vaccine industry advocated the introduction of Human Papillomavirus (HPV vaccine for the primary prevention of cervical cancer. Meanwhile, a local study suggested that the vaccine was considerably less cost-effective than cervical cancer screening in the Thai context. Then, from August to December 2008, the MoPH carried out a campaign to expand the coverage of its cervical cancer screening program, targeting one million women. The study reveals that several factors were influential in focusing the attention of policymakers on strengthening the screening services. These included the high burden of cervical cancer in Thailand, the launch of the HPV vaccine onto the global and domestic markets, the country’s political instability, and the dissemination of scientific evidence regarding the appropriateness of different options for cervical cancer prevention. Influenced by the country’s political crisis, the MoPH’s campaign was devised in a very short time. In the view of the responsible health officials, the campaign was not successful and indeed, did not achieve its ambitious target. Conclusion The Thai case study suggests that the political crisis was a

  19. Process engineering and scale-up of autotrophic Clostridium strain P11 syngas fermentation

    Science.gov (United States)

    Kundiyana, Dimple Kumar Aiyanna

    Scope and Method of Study. Biomass gasification followed by fermentation of syngas to ethanol is a potential process to produce bioenergy. The process is currently being researched under laboratory- and pilot-scale in an effort to optimize the process conditions and make the process feasible for commercial production of ethanol and other biofuels such as butanol and propanol. The broad research objectives for the research were to improve ethanol yields during syngas fermentation and to design a economical fermentation process. The research included four statistically designed experimental studies in serum bottles, bench-scale and pilot-scale fermentors to screen alternate fermentation media components, to determine the effect of process parameters such as pH, temperature and buffer on syngas fermentation, to determine the effect of key limiting nutrients of the acetyl-CoA pathway in a continuous series reactor design, and to scale-up the syngas fermentation in a 100-L pilot scale fermentor. Findings and Conclusions. The first experimental study identified cotton seed extract (CSE) as a feasible medium for Clostridium strain P11 fermentation. The study showed that CSE at 0.5 g L-1 can potentially replace all the standard Clostridium strain P11 fermentation media components while using a media buffer did not significantly improve the ethanol production when used in fermentation with CSE. Scale-up of the CSE fermentation in 2-L and 5-L stirred tank fermentors showed 25% increase in ethanol yield. The second experimental study showed that syngas fermentation at 32°C without buffer was associated with higher ethanol concentration and reduced lag time in switching to solventogenesis. Conducting fermentation at 40°C or by lowering incubation pH to 5.0 resulted in reduced cell growth and no production of ethanol or acetic acid. The third experiment studied the effect of three limiting nutrients, calcium pantothenate, vitamin B12 and CoCl2 on syngas fermentation. Results

  20. Non-isothermal flow of viscous liquids: engineering correlations for scale-up guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Dey, A.K.

    1988-10-01

    Measurements of pressure distribution and temperature distribution along the length of model pipeline test rigs were made at varying operating variables for laminar flow of newtonion and power-law liquids. Flow data were also collected for different concentrations of Sobhason Field crude oil mixed with various mixtures of petroleum products. The pressure gradient was found to vary with the length of pipe. The departure of the results from a Poiseuille type equation were examined in the light of related information available in the literature. The selection of proper operating variables could reduce power consumption substantially. The relationships developed from experimental results for a varying range of non-isothermal parameters based on inlet condition and ambient temperature acclaimed importance to scale up in designing pipelines for a given flow rate or pressure drop under variable heat flux conditions. 11 figs., 10 refs., 3 tabs.

  1. Experimental and scale up study of the flame spread over the PMMA sheets

    Directory of Open Access Journals (Sweden)

    Mamourian Mojtaba

    2009-01-01

    Full Text Available To explore the flame spread mechanisms over the solid fuel sheets, downward flame spread over vertical polymethylmethacrylate sheets with thicknesses from 1.75 to 5.75 mm have been examined in the quiescent environment. The dependence of the flame spread rate on the thickness of sheets is obtained by one-dimensional heat transfer model. An equation for the flame spread rate based on the thermal properties and the thickness of the sheet by scale up method is derived from this model. During combustion, temperature within the gas and solid phases is measured by a fine thermocouple. The pyrolysis temperature, the length of the pyrolysis zone, the length of the preheating zone, and the flame temperature are determined from the experimental data. Mathematical analysis has yielded realistic results. This model provides a useful formula to predict the rate of flame spread over any thin solid fuel.

  2. Drug nanocrystals: four basic prerequisites for formulation development and scale-up.

    Science.gov (United States)

    Srivalli, Kale Mohana Raghava; Mishra, Brahmeshwar

    2015-01-01

    Drug nanocrystals have been studied since the 1990s and there are already six therapeutic nanocrystal products on market and many more in clinical trials. Nanocrystals are encapsulating-carrier free nanoparticles wherein 100% drug loading could be achieved. This signifies that nanocrystals, among other nanoparticulate products, could be more easily manufactured even at the initial formulation development stages to evaluate the effect of size reduction on the bioavailability of drugs. Additionally, a drug nanocrystal is considered not as a generic product but as a "new drug" by FDA. Process characterization, equipment choice, robust formulation and stability are discussed as four basic prerequisites for formulation development and scale-up of drug nanocrystals. The fast growing and relatively superior market profile of nanocrystals amongst other nanoparticle systems is due to their rational formulation design and production simplicity. In this emerging scenario, keeping an eye on the four basic prerequisites can further improve the success of drug nanocrystals.

  3. Forest ecosystems and environments scaling up from shoot module to watershed

    CERN Document Server

    Kohyama, Takashi; Ojima, Dennis S

    2005-01-01

    Coastal East and Southeast Asia are characterized by wet growing seasons, and species-rich forest ecosystems develop throughout the latitudinal and altitudinal gradients. In this region, the Global Change Impacts on Terrestrial Ecosystems in Monsoon Asia (TEMA) project was carried out as a unique contribution to the international project Global Change and Terrestrial Ecosystems. TEMA aimed to integrate forest ecosystem processes, from leaf physiology to meteorological budget and prediction of long-term change of vegetation composition and architecture through demographic processes. Special attention was given to watershed processes, where forest ecosystem metabolism affects the properties and biogeochemical budgets of freshwater ecosystems, and where rivers, wetlands, and lakes are subject to direct and indirect effects of environmental change. This volume presents the scaling-up concept for better understanding of ecosystem functioning.

  4. Scaling up the health workforce in the public sector: the role of government fiscal policy.

    Science.gov (United States)

    Vujicic, Marko

    2010-01-01

    Health workers play a key role in increasing access to health care services. Global and country-level estimates show that staffing in many developing countries - particularly in Sub-Saharan Africa - is far leaner than needed to deliver essential health services to the population. One factor that can limit scaling up the health workforce in developing countries is the government's overall wage policy which sometimes creates restrictions on hiring in the health sector. But while there is considerable debate, the information base in this important area has been quite limited. This paper summarizes the process that determines the budget for health wages in the public sector, how it is linked to overall wage policies, and how this affects staffing in the health sector. The author draws mainly from a recent World Bank report.

  5. Evaluation of liquid-fed ceramic melter scale-up correlations

    Energy Technology Data Exchange (ETDEWEB)

    Koegler, S.S.; Mitchell, S.J.

    1988-08-01

    This study was conducted to determine the parameters governing factors of scale for liquid-fed ceramic melters (LFCMs) in order to design full-scale melters using smaller-scale melter data. Results of melter experiments conducted at Pacific Northwest Laboratory (PNL) and Savannah River Laboratory (SRL) are presented for two feed compositions and five different liquid-fed ceramic melters. The melter performance data including nominal feed rate and glass melt rate are correlated as a function of melter surface area. Comparisons are made between the actual melt rate data and melt rates predicted by a cold cap heat transfer model. The heat transfer model could be used in scale-up calculations, but insufficient data are available on the cold cap characteristics. Experiments specifically designed to determine heat transfer parameters are needed to further develop the model. 17 refs.

  6. 3D printed high-throughput hydrothermal reactionware for discovery, optimization, and scale-up.

    Science.gov (United States)

    Kitson, Philip J; Marshall, Ross J; Long, Deliang; Forgan, Ross S; Cronin, Leroy

    2014-11-17

    3D printing techniques allow the laboratory-scale design and production of reactionware tailored to specific experimental requirements. To increase the range and versatility of reactionware devices, sealed, monolithic reactors suitable for use in hydrothermal synthesis have been digitally designed and realized. The fabrication process allows the introduction of reaction mixtures directly into the reactors during the production, and also enables the manufacture of devices of varying scales and geometries unavailable in traditional equipment. The utility of these devices is shown by the use of 3D printed, high-throughput array reactors to discover two new coordination polymers, optimize the synthesis of one of these, and scale-up its synthesis using larger reactors produced on the same 3D printer. Reactors were also used to produce phase-pure samples of coordination polymers MIL-96 and HKUST-1, in yields comparable to synthesis in traditional apparatus. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Scale-up of Multidrug-Resistant Tuberculosis Laboratory Services, Peru

    Science.gov (United States)

    Yagui, Martin; Ascencios, Luis; Yale, Gloria; Suarez, Carmen; Quispe, Neyda; Bonilla, Cesar; Blaya, Joaquin; Taylor, Allison; Contreras, Carmen; Cegielski, Peter

    2008-01-01

    Over the past 10 years, the Peruvian National Tuberculosis (TB) Program, the National Reference Laboratory (NRL), Socios en Salud, and US partners have worked to strengthen the national TB laboratory network to support treatment of multidrug-resistant TB. We review key lessons of this experience. The preparation phase involved establishing criteria for drug susceptibility testing (DST), selecting appropriate DST methods, projecting the quantity of DST and culture to ensure adequate supplies, creating biosafe laboratory facilities for DST, training laboratory personnel on methods, and validating DST methods at the NRL. Implementation involved training providers on DST indications, validating conventional and rapid first-line DST methods at district laboratories, and eliminating additional delays in specimen transport and result reporting. Monitoring included ongoing quality control and quality assurance procedures. Hurdles included logistics, coordinating with policy, competing interests, changing personnel, communications, and evaluation. Operational research guided laboratory scale-up and identified barriers to effective capacity building. PMID:18439349

  8. Scaling-up vaccine production: implementation aspects of a biomass growth observer and controller.

    Science.gov (United States)

    Soons, Zita I T A; van den IJssel, Jan; van der Pol, Leo A; van Straten, Gerrit; van Boxtel, Anton J B

    2009-04-01

    This study considers two aspects of the implementation of a biomass growth observer and specific growth rate controller in scale-up from small- to pilot-scale bioreactors towards a feasible bulk production process for whole-cell vaccine against whooping cough. The first is the calculation of the oxygen uptake rate, the starting point for online monitoring and control of biomass growth, taking into account the dynamics in the gas-phase. Mixing effects and delays are caused by amongst others the headspace and tubing to the analyzer. These gas phase dynamics are modelled using knowledge of the system in order to reconstruct oxygen consumption. The second aspect is to evaluate performance of the monitoring and control system with the required modifications of the oxygen consumption calculation on pilot-scale. In pilot-scale fed-batch cultivation good monitoring and control performance is obtained enabling a doubled concentration of bulk vaccine compared to standard batch production.

  9. Scaling-up of membraneless microbial electrolysis cells (MECs) for domestic wastewater treatment: Bottlenecks and limitations.

    Science.gov (United States)

    Escapa, A; San-Martín, M I; Mateos, R; Morán, A

    2015-03-01

    Microbial electrolysis cells (MECs) have the potential to become a sustainable domestic wastewater (dWW) treatment system. However, new scale-up experiences are required to gain knowledge of critical issues in MEC designs. In this study we assess the ability of two twin membraneless MEC units (that are part of a modular pilot-scale MEC) to treat dWW. Batch tests yielded COD removal efficiencies as high as 92%, with most of the hydrogen (>80% of the total production) being produced during the first 48h. During the continuous tests, MECs performance deteriorated significantly (energy consumption was relatively high and COD removal efficiencies fell below 10% in many cases), which was attributed to an inadequate configuration of the anodic chamber, insufficient mixing inside this chamber, inefficient hydrogen management on the cathode side and finally to dWW in itself. Some alternatives to the current design are suggested. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Geriatric health policy in India: The need for scaling-up implementation

    Directory of Open Access Journals (Sweden)

    N Sherin Susan Paul

    2016-01-01

    Full Text Available In an anticipation of the rising geriatric population in India, the Central government constituted the National Policy for Older Persons in 1999 to promote the health and welfare of senior citizens in India. A major strategy of this policy is to encourage families to take care of their older family members. The policy also encourages voluntary organizations to supplement the care provided by the family and provide care and protection to vulnerable elderly people. The implementation of this policy, particularly in the rural areas, has been negligible and calls for a scaling-up of programs to address the physical, psychological, and social needs of the poor. Due to breakdown of the joint family system and the migration of the younger generation to the towns and cities, the elderly parents in the villages are left to fend for themselves. Too old to work and with little or no source of income, the elders are struggling even to satisfy their basic needs. This article primarily focuses on the various facets of elderly care in India. As a fledgling nation in elderly care, we should take cues from other nations who have pioneered in this field and should constantly evolve to identify and face the various challenges that come up, especially from rural India. The Rural Unit for Health and Social Affairs Department of a well-known Medical College in South India has developed a “senior recreation day care” model which proves to be a useful replicable model to improve the quality of life and nutritional status of the elderly in the lower rungs of society. More than a decade since its inception, it is now the right time to assess the implementation of our geriatric health policy and scale-up programs so that the elderly in our country, irrespective of urban and rural, will have a dignified and good quality life.

  11. Liposome and niosome preparation using a membrane contactor for scale-up.

    Science.gov (United States)

    Pham, Thi Thuy; Jaafar-Maalej, Chiraz; Charcosset, Catherine; Fessi, Hatem

    2012-06-01

    The scaling-up ability of liposome and niosome production, from laboratory scale using a syringe-pump device to a pilot scale using the membrane contactor module, was investigated. For this aim, an ethanol injection-based method was applied for liposome and niosome preparation. The syringe-pump device was used for laboratory scale batches production (30 ml for liposomes, 20 ml for niosomes) then a pilot scale (750 ml for liposomes, 1000 ml for niosomes) were obtained using the SPG membrane contactor. Resulted nanovesicles were characterized in terms of mean vesicles size, polydispersity index (PdI) and zeta potential. The drug encapsulation efficiency (E.E.%) was evaluated using two drug-models: caffeine and spironolactone, a hydrophilic and a lipophilic molecule, respectively. As results, nanovectors mean size using the syringe-pump device was comprised between 82 nm and 95 nm for liposomes and between 83 nm and 127 nm for niosomes. The optimal E.E. of caffeine within niosomes, was found around 9.7% whereas the spironolactone E.E. reached 95.6% which may be attributed to its lipophilic properties. For liposomes these values were about 9.7% and 86.4%, respectively. It can be clearly seen that the spironolactone E.E. was slightly higher within niosomes than liposomes. Optimized formulations, which offered smaller size and higher E.E., were selected for pilot scale production using the SPG membrane. It has been found that vesicles characteristics (size and E.E.%) were reproducible using the membrane contactor module. Thus, the current study demonstrated the usefulness of the membrane contactor as a device for scaling-up both liposome and niosome preparations with small mean sizes. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Manufacturing process scale-up of optical grade transparent spinel ceramic at ArmorLine Corporation

    Science.gov (United States)

    Spilman, Joseph; Voyles, John; Nick, Joseph; Shaffer, Lawrence

    2013-06-01

    While transparent Spinel ceramic's mechanical and optical characteristics are ideal for many Ultraviolet (UV), visible, Short-Wave Infrared (SWIR), Mid-Wave Infrared (MWIR), and multispectral sensor window applications, commercial adoption of the material has been hampered because the material has historically been available in relatively small sizes (one square foot per window or less), low volumes, unreliable supply, and with unreliable quality. Recent efforts, most notably by Technology Assessment and Transfer (TA and T), have scaled-up manufacturing processes and demonstrated the capability to produce larger windows on the order of two square feet, but with limited output not suitable for production type programs. ArmorLine Corporation licensed the hot-pressed Spinel manufacturing know-how of TA and T in 2009 with the goal of building the world's first dedicated full-scale Spinel production facility, enabling the supply of a reliable and sufficient volume of large Transparent Armor and Optical Grade Spinel plates. With over $20 million of private investment by J.F. Lehman and Company, ArmorLine has installed and commissioned the largest vacuum hot press in the world, the largest high-temperature/high-pressure hot isostatic press in the world, and supporting manufacturing processes within 75,000 square feet of manufacturing space. ArmorLine's equipment is capable of producing window blanks as large as 50" x 30" and the facility is capable of producing substantial volumes of material with its Lean configuration and 24/7 operation. Initial production capability was achieved in 2012. ArmorLine will discuss the challenges that were encountered during scale-up of the manufacturing processes, ArmorLine Optical Grade Spinel optical performance, and provide an overview of the facility and its capabilities.

  13. UPC Scaling-up methodology for Deterministic Safety Assessment and Support to Plant Operation

    Energy Technology Data Exchange (ETDEWEB)

    Martínez-Quiroga, V.; Reventós, F.; Batet, Il.

    2015-07-01

    Best Estimate codes along with necessary nodalizations are widely used tools in nuclear engineering for both Deterministic Safety Assessment (DSA) and Support to Plant Operation and Control. In this framework, the application of quality assurance procedures in both codes and nodalizations becomes an essential step prior any significant study. Along these lines the present paper introduces the UPC SCUP, a systematic methodology based on the extrapolation of the Integral Test Facilities (ITF) post-test simulations by means of scaling analyses. In that sense, SCUP fulfills a gap in current nodalization qualification procedures, the related with the validation of NPP nodalizations for Design Basis Accidents conditions. Three are the pillars that support SCUP: judicial selection of the experimental transients, full confidence in the quality of the ITF simulations, and simplicity in justifying discrepancies that appear between ITF and NPP counterpart transients. The techniques that are presented include the socalled Kv scaled calculations as well as the use of two new approaches, ”Hybrid nodalizations” and ”Scaled-up nodalizations”. These last two methods have revealed themselves to be very helpful in producing the required qualification and in promoting further improvements in nodalization. The study of both LSTF and PKL counterpart tests have allowed to qualify the methodology by the comparison with experimental data. Post-test simulations at different sizes allowed to define which phenomena could be well reproduced by system codes and which not, in this way also establishing the basis for the extrapolation to an NPP scaled calculation. Furthermore, the application of the UPC SCUP methodology demonstrated that selected phenomena can be scaled-up and explained between counterpart simulations by carefully considering the differences in scale and design. (Author)

  14. High-Throughput Synthesis, Screening, and Scale-Up of Optimized Conducting Indium Tin Oxides.

    Science.gov (United States)

    Marchand, Peter; Makwana, Neel M; Tighe, Christopher J; Gruar, Robert I; Parkin, Ivan P; Carmalt, Claire J; Darr, Jawwad A

    2016-02-08

    A high-throughput optimization and subsequent scale-up methodology has been used for the synthesis of conductive tin-doped indium oxide (known as ITO) nanoparticles. ITO nanoparticles with up to 12 at % Sn were synthesized using a laboratory scale (15 g/hour by dry mass) continuous hydrothermal synthesis process, and the as-synthesized powders were characterized by powder X-ray diffraction, transmission electron microscopy, energy-dispersive X-ray analysis, and X-ray photoelectron spectroscopy. Under standard synthetic conditions, either the cubic In2O3 phase, or a mixture of InO(OH) and In2O3 phases were observed in the as-synthesized materials. These materials were pressed into compacts and heat-treated in an inert atmosphere, and their electrical resistivities were then measured using the Van der Pauw method. Sn doping yielded resistivities of ∼ 10(-2) Ω cm for most samples with the lowest resistivity of 6.0 × 10(-3) Ω cm (exceptionally conductive for such pressed nanopowders) at a Sn concentration of 10 at %. Thereafter, the optimized lab-scale composition was scaled-up using a pilot-scale continuous hydrothermal synthesis process (at a rate of 100 g/hour by dry mass), and a comparable resistivity of 9.4 × 10(-3) Ω cm was obtained. The use of the synthesized TCO nanomaterials for thin film fabrication was finally demonstrated by deposition of a transparent, conductive film using a simple spin-coating process.

  15. Changing cost of HIV interventions in the context of scaling-up in India.

    Science.gov (United States)

    Dandona, Lalit; Kumar, Sg Prem; Ramesh, Yk; Rao, M Chalapathi; Kumar, A Anod; Marseille, Elliot; Kahn, James G; Dandona, Rakhi

    2008-07-01

    A rapid scaling up of HIV interventions in India is anticipated, but systematic information on how costs of HIV interventions change over time and programme scale is not available to inform planning. We studied the changes in unit costs of two major interventions, voluntary counseling and testing (VCT) and sex worker programmes in the south Indian state of Andhra Pradesh between 2002-2003 and 2005-2006 fiscal years. Economic costs (from the provider perspective) and output data from 17 publicly funded VCT centers and 14 sex worker programmes were collected using standardized methods. We calculated unit costs for each programme in each period and explored possible reasons for the changes seen. In 2005-2006, the VCT centers served 66 445 clients and the sex worker programmes served 32 550. The unit cost of providing VCT dropped over 3 years by half to Indian Rupees (INR) 147.5 (US$3.33) mainly because the number of clients doubled. There was no decrease in the average time spent counseling each client. The unit cost of providing services to sex workers increased 2.4 times over 3 years to INR 1401 (US$31.6) as a result of increases in male condom distribution, staff salaries and training, and treatment for sexually transmitted infections, all suggesting improved services. The unit cost of these two interventions changed dramatically over a 3-year period, but in opposite directions. The current unit cost for VCT in Andhra Pradesh is much lower than the estimated global average for low-income settings. These local longitudinal cost data are useful to inform the currently planned scaling up of HIV interventions in India.

  16. Peruvian Mental Health Reform: A Framework for Scaling-up Mental Health Services

    Directory of Open Access Journals (Sweden)

    Mauricio Toyama

    2017-09-01

    Full Text Available Background Mental, neurological, and substance (MNS use disorders are a leading cause of disability worldwide; specifically in Peru, MNS affect 1 in 5 persons. However, the great majority of people suffering from these disorders do not access care, thereby making necessary the improvement of existing conditions including a major rearranging of current health system structures beyond care delivery strategies. This paper reviews and examines recent developments in mental health policies in Peru, presenting an overview of the initiatives currently being introduced and the main implementation challenges they face. Methods Key documents issued by Peruvian governmental entities regarding mental health were reviewed to identify and describe the path that led to the beginning of the reform; how the ongoing reform is taking place; and, the plan and scope for scale-up. Results Since 2004, mental health has gained importance in policies and regulations, resulting in the promotion of a mental health reform within the national healthcare system. These efforts crystallized in 2012 with the passing of Law 29889 which introduced several changes to the delivery of mental healthcare, including a restructuring of mental health service delivery to occur at the primary and secondary care levels and the introduction of supporting services to aid in patient recovery and reintegration into society. In addition, a performance-based budget was approved to guarantee the implementation of these changes. Some of the main challenges faced by this reform are related to the diversity of the implementation settings, eg, isolated rural areas, and the limitations of the existing specialized mental health institutes to substantially grow in parallel to the scaling-up efforts in order to be able to provide training and clinical support to every region of Peru. Conclusion Although the true success of the mental healthcare reform will be determined in the coming years, thus far, Peru

  17. Scale-up guidelines for a circulating fluidized bed biomass pyrolyzer

    Energy Technology Data Exchange (ETDEWEB)

    Haslinger, W.; Hofbauer, H. [Technische Univ., Vienna (Austria); Gavriil, L.; Boukis, I. [Center for Renewable Energy Sources (Greece)

    1999-07-01

    A new circulating fluidized bed design has been proposed and successfully operated at lab scale (10 kg/h biomass feed). This fluidized bed system consists of a bubbling bottom bed, above this bottom bed a riser, a cyclone and a return leg. The heat necessary for the pyrolysis process is produced in the bottom bed by burning some solid residue from the pyrolysis that circulates together with the bed material as the bottom bed is fluidized with air. The flue gas from the bottom bed enters into the riser and serves there as transport gas. The circulation rate is very sensitive to the amount of bed inventory and the fluidization velocities. As the riser uses the flue gas of the dense bottom bed the ratio of the cross sections of the two fluidized beds has to be in a certain range to get a satisfying operation. The fluid mechanic behavior of this new circulating fluidized bed pyrolyzer has been studied using three different cold flow models. One cold flow model was built for the existing 10 kg/h lab scale pyrolyzer according to Glicksman's (1984) similarity rules. The purpose of this cold model was to study the fluid mechanics and optimize the performance with respect to the pyrolysis process. For scale-up purposes further cold flow models (135 kg/h, 1000 kg/h) have been designed, built and investigated intensively. The idea and the new design of the pyrolyzer, the results of the experimental work as well as the scale-up criteria will be presented. (orig.)

  18. Peruvian Mental Health Reform: A Framework for Scaling-up Mental Health Services

    Science.gov (United States)

    Toyama, Mauricio; Castillo, Humberto; Galea, Jerome T.; Brandt, Lena R.; Mendoza, María; Herrera, Vanessa; Mitrani, Martha; Cutipé, Yuri; Cavero, Victoria; Diez-Canseco, Francisco; Miranda, J. Jaime

    2017-01-01

    Background: Mental, neurological, and substance (MNS) use disorders are a leading cause of disability worldwide; specifically in Peru, MNS affect 1 in 5 persons. However, the great majority of people suffering from these disorders do not access care, thereby making necessary the improvement of existing conditions including a major rearranging of current health system structures beyond care delivery strategies. This paper reviews and examines recent developments in mental health policies in Peru, presenting an overview of the initiatives currently being introduced and the main implementation challenges they face. Methods: Key documents issued by Peruvian governmental entities regarding mental health were reviewed to identify and describe the path that led to the beginning of the reform; how the ongoing reform is taking place; and, the plan and scope for scale-up. Results: Since 2004, mental health has gained importance in policies and regulations, resulting in the promotion of a mental health reform within the national healthcare system. These efforts crystallized in 2012 with the passing of Law 29889 which introduced several changes to the delivery of mental healthcare, including a restructuring of mental health service delivery to occur at the primary and secondary care levels and the introduction of supporting services to aid in patient recovery and reintegration into society. In addition, a performance-based budget was approved to guarantee the implementation of these changes. Some of the main challenges faced by this reform are related to the diversity of the implementation settings, eg, isolated rural areas, and the limitations of the existing specialized mental health institutes to substantially grow in parallel to the scaling-up efforts in order to be able to provide training and clinical support to every region of Peru. Conclusion: Although the true success of the mental healthcare reform will be determined in the coming years, thus far, Peru has achieved a

  19. Scale up of 2,4-dichlorophenol removal from aqueous solutions using Brassica napus hairy roots

    Energy Technology Data Exchange (ETDEWEB)

    Angelini, Vanina A. [Departamento de Biologia Molecular, FCEFQN, Universidad Nacional de Rio Cuarto, 5800 Rio Cuarto, Cordoba (Argentina); Orejas, Joaquin [Facultad de Ingenieria, Universidad Nacional de Rio Cuarto, 5800 Rio Cuarto, Cordoba (Argentina); Medina, Maria I. [Departamento de Biologia Molecular, FCEFQN, Universidad Nacional de Rio Cuarto, 5800 Rio Cuarto, Cordoba (Argentina); Agostini, Elizabeth, E-mail: eagostini@exa.unrc.edu.ar [Departamento de Biologia Molecular, FCEFQN, Universidad Nacional de Rio Cuarto, 5800 Rio Cuarto, Cordoba (Argentina)

    2011-01-15

    Research highlights: {yields}B. napus hairy roots were effectively used for a large scale removal of 2,4-DCP. {yields} High removal efficiencies were obtained (98%) in a short time (30 min). {yields} Roots were re-used for six consecutive cycles with high efficiency. {yields} Post removal solutions showed no toxicity. {yields} This method could be used for continuous and safe treatment of phenolic effluents. - Abstract: Chlorophenols are harmful pollutants, frequently found in the effluents of several industries. For this reason, many environmental friendly technologies are being explored for their removal from industrial wastewaters. The aim of the present work was to study the scale up of 2,4-dichlorophenol (2,4-DCP) removal from synthetic wastewater, using Brassica napus hairy roots and H{sub 2}O{sub 2} in a discontinuous stirred tank reactor. We have analyzed some operational conditions, because the scale up of such process was poorly studied. High removal efficiencies were obtained (98%) in a short time (30 min). When roots were re-used for six consecutive cycles, 2,4-DCP removal efficiency decreased from 98 to 86%, in the last cycle. After the removal process, the solutions obtained from the reactor were assessed for their toxicity using an acute test with Lactuca sativa L. seeds. Results suggested that the treated solution was less toxic than the parent solution, because neither inhibition of lettuce germination nor effects in root and hypocotyl lengths were observed. Therefore, we provide evidence that Brassica napus hairy roots could be effectively used to detoxify solutions containing 2,4-DCP and they have considerable potential for a large scale removal of this pollutant. Thus, this study could help to design a method for continuous and safe treatment of effluents containing chlorophenols.

  20. Scale-down/scale-up studies leading to improved commercial beer fermentation.

    Science.gov (United States)

    Nienow, Alvin W; Nordkvist, Mikkel; Boulton, Christopher A

    2011-08-01

    Scale-up/scale-down techniques are vital for successful and safe commercial-scale bioprocess design and operation. An example is given in this review of recent studies related to beer production. Work at the bench scale shows that brewing yeast is not compromised by mechanical agitation up to 4.5 W/kg; and that compared with fermentations mixed by CO(2) evolution, agitation ≥ 0.04 W/kg is able to reduce fermentation time by about 20%. Work at the commercial scale in cylindroconical fermenters shows that, without mechanical agitation, most of the yeast sediments into the cone for about 50% of the fermentation time, leading to poor temperature control. Stirrer mixing overcomes these problems and leads to a similar reduction in batch time as the bench-scale tests and greatly reduces its variability, but is difficult to install in extant fermenters. The mixing characteristics of a new jet mixer, a rotary jet mixer, which overcomes these difficulties, are reported, based on pilot-scale studies. This change enables the advantages of stirring to be achieved at the commercial scale without the problems. In addition, more of the fermentable sugars are converted into ethanol. This review shows the effectiveness of scale-up/scale-down studies for improving commercial operations. Suggestions for further studies are made: one concerning the impact of homogenization on the removal of vicinal diketones and the other on the location of bubble formation at the commercial scale. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Minnesota wood energy scale-up project 1994 establishment cost data

    Energy Technology Data Exchange (ETDEWEB)

    Downing, M. [Oak Ridge National Lab., TN (United States); Pierce, R. [Champion International, Alexandria, MN (United States); Kroll, T. [Minnesota Department of Natural Resources-Forestry, St. Cloud, MN (United States)

    1996-03-18

    The Minnesota Wood Energy Scale-up Project began in late 1993 with the first trees planted in the spring of 1994. The purpose of the project is to track and monitor economic costs of planting, maintaining and monitoring larger scale commercial plantings. For 15 years, smaller scale research plantings of hybrid poplar have been used to screen for promising, high-yielding poplar clones. In this project 1000 acres of hybrid poplar trees were planted on Conservation Reserve Program (CRP) land near Alexandria, Minnesota in 1994. The fourteen landowners involved re-contracted with the CRP for five-year extensions of their existing 10-year contracts. These extended contracts will expire in 2001, when the plantings are 7 years old. The end use for the trees planted in the Minnesota Wood Energy Scale-up Project is undetermined. They will belong to the owner of the land on which they are planted. There are no current contracts in place for the wood these trees are projected to supply. The structure of the wood industry in the Minnesota has changed drastically over the past 5 years. Stumpage values for fiber have risen to more than $20 per cord in some areas raising the possibility that these trees could be used for fiber rather than energy. Several legislative mandates have forced the State of Minnesota to pursue renewable energy including biomass energy. These mandates, a potential need for an additional 1700 MW of power by 2008 by Northern States Power, and agricultural policies will all affect development of energy markets for wood produced much like agricultural crops. There has been a tremendous amount of local and international interest in the project. Contractual negotiations between area landowners, the CRP, a local Resource Conservation and Development District, the Minnesota Department of Natural Resources and others are currently underway for additional planting of 1000 acres in spring 1995.

  2. Prototype of a scaled-up microbial fuel cell for copper recovery.

    Science.gov (United States)

    Rodenas Motos, Pau; Molina, Gonzalo; Ter Heijne, Annemiek; Sleutels, Tom; Saakes, Michel; Buisman, Cees

    2017-11-01

    Bioelectrochemical systems (BESs) enable recovery of electrical energy through oxidation of a wide range of substrates at an anode and simultaneous recovery of metals at a cathode. Scale-up of BESs from the laboratory to pilot scale is a challenging step in the development of the process, and there are only a few successful experiences to build on. This paper presents a prototype BES for the recovery of copper. The cell design presented here had removable electrodes, similar to those in electroplating baths. The anode and cathode in this design could be replaced independently. The prototype bioelectrochemical cell consisted of an 835 cm2 bioanode fed with acetate, and a 700 cm2 cathode fed with copper. A current density of 1.2 A/-2 was achieved with 48 mW m-2 of power production. The contribution of each component (anode, electrolytes, cathode and membrane) was evaluated through the analysis of the internal resistance distribution. This revealed that major losses occurred at the anode, and that the design with removable electrodes results in higher internal resistance compared with other systems. To further assess the practical applicability of BES for copper recovery, an economic evaluation was performed. Analysis shows that the internal resistance of several lab-scale BESs is already sufficiently low to make the system economic, while the internal resistance for scaled-up systems still needs to be improved considerably to become economically applicable.© 2017 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

  3. LOGISMOS-B for primates: primate cortical surface reconstruction and thickness measurement

    Science.gov (United States)

    Oguz, Ipek; Styner, Martin; Sanchez, Mar; Shi, Yundi; Sonka, Milan

    2015-03-01

    Cortical thickness and surface area are important morphological measures with implications for many psychiatric and neurological conditions. Automated segmentation and reconstruction of the cortical surface from 3D MRI scans is challenging due to the variable anatomy of the cortex and its highly complex geometry. While many methods exist for this task in the context of the human brain, these methods are typically not readily applicable to the primate brain. We propose an innovative approach based on our recently proposed human cortical reconstruction algorithm, LOGISMOS-B, and the Laplace-based thickness measurement method. Quantitative evaluation of our approach was performed based on a dataset of T1- and T2-weighted MRI scans from 12-month-old macaques where labeling by our anatomical experts was used as independent standard. In this dataset, LOGISMOS-B has an average signed surface error of 0.01 +/- 0.03mm and an unsigned surface error of 0.42 +/- 0.03mm over the whole brain. Excluding the rather problematic temporal pole region further improves unsigned surface distance to 0.34 +/- 0.03mm. This high level of accuracy reached by our algorithm even in this challenging developmental dataset illustrates its robustness and its potential for primate brain studies.

  4. Scaling up kangaroo mother care in South Africa: 'on-site' versus 'off-site' educational facilitation

    National Research Council Canada - National Science Library

    Bergh, Anne-Marie; van Rooyen, Elise; Pattinson, Robert C

    2008-01-01

    .... This paper reports on the results of testing the effectiveness of two different kinds of face-to-face facilitation used in conjunction with a well-designed educational package in the scaling up of kangaroo mother care...

  5. Constraints, synergies and avenues for scaling up breastfeeding, antibiotics for pneumonia and IMCI interventions in the Cusco region, Peru

    National Research Council Canada - National Science Library

    Sarganas, Giselle; Scherpbier, Robert; Gericke, Christian A

    2012-01-01

    Objective: The purpose of this qualitative case study was to assess the feasibility of scaling up exclusive breastfeeding for 6 months, antibiotics for pneumonia and integrated management of childhood illness (IMCI...

  6. Constraints, synergies and avenues for scaling up breastfeeding, antibiotics for pneumonia and IMCI interventions in the Cusco region, Peru

    National Research Council Canada - National Science Library

    Sarganas, Giselle; Scherpbier, Robert; Gericke, Christian A

    2012-01-01

    The purpose of this qualitative case study was to assess the feasibility of scaling up exclusive breastfeeding for 6 months, antibiotics for pneumonia and integrated management of childhood illness (IMCI...

  7. Do we have the right models for scaling up health services to achieve the Millennium Development Goals?

    Directory of Open Access Journals (Sweden)

    Subramanian Savitha

    2011-12-01

    Full Text Available Abstract Background There is widespread agreement on the need for scaling up in the health sector to achieve the Millennium Development Goals (MDGs. But many countries are not on track to reach the MDG targets. The dominant approach used by global health initiatives promotes uniform interventions and targets, assuming that specific technical interventions tested in one country can be replicated across countries to rapidly expand coverage. Yet countries scale up health services and progress against the MDGs at very different rates. Global health initiatives need to take advantage of what has been learned about scaling up. Methods A systematic literature review was conducted to identify conceptual models for scaling up health in developing countries, with the articles assessed according to the practical concerns of how to scale up, including the planning, monitoring and implementation approaches. Results We identified six conceptual models for scaling up in health based on experience with expanding pilot projects and diffusion of innovations. They place importance on paying attention to enhancing organizational, functional, and political capabilities through experimentation and adaptation of strategies in addition to increasing the coverage and range of health services. These scaling up approaches focus on fostering sustainable institutions and the constructive engagement between end users and the provider and financing organizations. Conclusions The current approaches to scaling up health services to reach the MDGs are overly simplistic and not working adequately. Rather than relying on blueprint planning and raising funds, an approach characteristic of current global health efforts, experience with alternative models suggests that more promising pathways involve "learning by doing" in ways that engage key stakeholders, uses data to address constraints, and incorporates results from pilot projects. Such approaches should be applied to current

  8. Scaling up kangaroo mother care in South Africa: 'on-site' versus 'off-site' educational facilitation

    OpenAIRE

    van Rooyen Elise; Bergh Anne-Marie; Pattinson Robert C

    2008-01-01

    Abstract Background Scaling up the implementation of new health care interventions can be challenging and demand intensive training or retraining of health workers. This paper reports on the results of testing the effectiveness of two different kinds of face-to-face facilitation used in conjunction with a well-designed educational package in the scaling up of kangaroo mother care. Methods Thirty-six hospitals in the Provinces of Gauteng and Mpumalanga in South Africa were targeted to implemen...

  9. Scaling Up of Breastfeeding Promotion Programs in Low- and Middle-Income Countries: the “Breastfeeding Gear” Model12

    OpenAIRE

    Pérez-Escamilla, Rafael; Curry, Leslie; Minhas, Dilpreet; Taylor, Lauren; Bradley, Elizabeth

    2012-01-01

    Breastfeeding (BF) promotion is one of the most cost-effective interventions to advance mother–child health. Evidence-based frameworks and models to promote the effective scale up and sustainability of BF programs are still lacking. A systematic review of peer-reviewed and gray literature reports was conducted to identify key barriers and facilitators for scale up of BF programs in low- and middle-income countries. The review identified BF programs located in 28 countries in Africa, Latin Ame...

  10. Human resources requirements for highly active antiretroviral therapy scale-up in Malawi

    Directory of Open Access Journals (Sweden)

    Rudatsikira Emmanuel

    2007-12-01

    nurses, 118.1% to 354.2% of all the available pharmacists and pharmacy technicians and 27.9% to 55.7% of all clinical officers and physicians. The actual number of health professionals working in the delivery of HAART in the clinics represented 44% to 88.8% (for clinical officers and medical doctors and 13.6% and 47.6% (for nurses, of what would have been needed based on the literature estimation. Conclusion HAART provision is a labour intensive exercise. Although these data are insufficient to determine whether HAART scale-up has resulted in the weakening or strengthening of the health systems in Malawi, the human resources requirements for HAART scale-up are significant. Malawi is using far less human resources than would be estimated based on the literature from other settings. The impact of HAART scale-up on the overall delivery of health services should be assessed.

  11. Current research on the organization and function of the visual system in primates

    Directory of Open Access Journals (Sweden)

    Kaas JH

    2014-09-01

    Full Text Available Jon H Kaas, Pooja Balaram Department of Psychology, Vanderbilt University, Nashville, TN, USAAll primates, including humans, are highly visual creatures.1–3 We rely heavily on visual cues for basic adaptive behaviors such as finding food, mates, and shelter; as well as more complex behaviors such as parental care and the formation of social hierarchies. Throughout the course of primate evolution, our dependence on visual cues has increased with each adaptive advantage acquired from visually guided behavior; and so has the demand for greater and more efficient processing of visual information in primate brains. Consequently, the number, size, and complexity of brain structures involved in visual processing has expanded dramatically in the primate order, far more than those of any other species in the mammalian lineage.2,4 As we have learned to interact with the world using visual cues, our brains have evolved to absorb, manipulate, and react to visual information in increasingly effective ways. Individual brain structures dedicated to vision in primates also frequently exhibit anatomical and functional specializations that are not present in other mammals. These adaptations are not present in most nonprimate mammals, partly because many species rely on other sensory modalities for their individual behaviors. Thus, understanding how we, as humans, perceive the visual world around us begins with learning how vision is processed in the primate brain. Furthermore, learning how vision in primates differs both structurally and functionally from vision in nonprimate mammals, and determining how those changes enable adaptive traits in the primate lineage, will allow us to understand the truly unique phenomenon of human visual behavior.

  12. Considerations for reducing food system energy demand while scaling up urban agriculture

    Science.gov (United States)

    Mohareb, Eugene; Heller, Martin; Novak, Paige; Goldstein, Benjamin; Fonoll, Xavier; Raskin, Lutgarde

    2017-12-01

    There is an increasing global interest in scaling up urban agriculture (UA) in its various forms, from private gardens to sophisticated commercial operations. Much of this interest is in the spirit of environmental protection, with reduced waste and transportation energy highlighted as some of the proposed benefits of UA; however, explicit consideration of energy and resource requirements needs to be made in order to realize these anticipated environmental benefits. A literature review is undertaken here to provide new insight into the energy implications of scaling up UA in cities in high-income countries, considering UA classification, direct/indirect energy pressures, and interactions with other components of the food–energy–water nexus. This is followed by an exploration of ways in which these cities can plan for the exploitation of waste flows for resource-efficient UA. Given that it is estimated that the food system contributes nearly 15% of total US energy demand, optimization of resource use in food production, distribution, consumption, and waste systems may have a significant energy impact. There are limited data available that quantify resource demand implications directly associated with UA systems, highlighting that the literature is not yet sufficiently robust to make universal claims on benefits. This letter explores energy demand from conventional resource inputs, various production systems, water/energy trade-offs, alternative irrigation, packaging materials, and transportation/supply chains to shed light on UA-focused research needs. By analyzing data and cases from the existing literature, we propose that gains in energy efficiency could be realized through the co-location of UA operations with waste streams (e.g. heat, CO2, greywater, wastewater, compost), potentially increasing yields and offsetting life cycle energy demands relative to conventional approaches. This begs a number of energy-focused UA research questions that explore the

  13. Task sharing in Zambia: HIV service scale-up compounds the human resource crisis

    LENUS (Irish Health Repository)

    Walsh, Aisling

    2010-09-17

    Abstract Background Considerable attention has been given by policy makers and researchers to the human resources for health crisis in Africa. However, little attention has been paid to quantifying health facility-level trends in health worker numbers, distribution and workload, despite growing demands on health workers due to the availability of new funds for HIV\\/AIDS control scale-up. This study analyses and reports trends in HIV and non-HIV ambulatory service workloads on clinical staff in urban and rural district level facilities. Methods Structured surveys of health facility managers, and health services covering 2005-07 were conducted in three districts of Zambia in 2008 (two urban and one rural), to fill this evidence gap. Intra-facility analyses were conducted, comparing trends in HIV and non-HIV service utilisation with staff trends. Results Clinical staff (doctors, nurses and nurse-midwives, and clinical officers) numbers and staff population densities fell slightly, with lower ratios of staff to population in the rural district. The ratios of antenatal care and family planning registrants to nurses\\/nurse-midwives were highest at baseline and increased further at the rural facilities over the three years, while daily outpatient department (OPD) workload in urban facilities fell below that in rural facilities. HIV workload, as measured by numbers of clients receiving antiretroviral treatment (ART) and prevention of mother to child transmission (PMTCT) per facility staff member, was highest in the capital city, but increased rapidly in all three districts. The analysis suggests evidence of task sharing, in that staff designated by managers as ART and PMTCT workers made up a higher proportion of frontline service providers by 2007. Conclusions This analysis of workforce patterns across 30 facilities in three districts of Zambia illustrates that the remarkable achievements in scaling-up HIV\\/AIDS service delivery has been on the back of sustained non

  14. Scaling up a Mobile Telemedicine Solution in Botswana: Keys to Sustainability.

    Science.gov (United States)

    Ndlovu, Kagiso; Littman-Quinn, Ryan; Park, Elizabeth; Dikai, Zambo; Kovarik, Carrie L

    2014-01-01

    Effective health care delivery is significantly compromised in an environment where resources, both human and technical, are limited. Botswana's health care system is one of the many in the African continent with few specialized medical doctors, thereby posing a barrier to patients' access to health care services. In addition, the traditional landline and non-robust Information Technology (IT) network infrastructure characterized by slow bandwidth still dominates the health care system in Botswana. Upgrading of the landline IT infrastructure to meet today's health care demands is a tedious, long, and expensive process. Despite these challenges, there still lies hope in health care delivery utilizing wireless telecommunication services. Botswana has recently experienced tremendous growth in the mobile telecommunication industry coupled with an increase in the number of individually owned mobile devices. This growth inspired the Botswana-UPenn Partnership (BUP) to collaborate with local partners to explore using mobile devices as tools to improve access to specialized health care delivery. Pilot studies were conducted across four medical specialties, including radiology, oral medicine, dermatology, and cervical cancer screening. Findings from the studies became vital evidence in support of the first scale-up project of a mobile telemedicine solution in Botswana, also known as "Kgonafalo." Some technical and social challenges were encountered during the initial studies, such as malfunctioning of mobile devices, accidental damage of devices, and cultural misalignment between IT and healthcare providers. These challenges brought about lessons learnt, including a strong need for unwavering senior management support, establishment of solid local public-private partnerships, and efficient project sustainability plans. Sustainability milestones included the development and signing of a Memorandum of Understanding (MOU) between the Botswana government and a private

  15. Task sharing in Zambia: HIV service scale-up compounds the human resource crisis

    Directory of Open Access Journals (Sweden)

    Simbaya Joseph

    2010-09-01

    Full Text Available Abstract Background Considerable attention has been given by policy makers and researchers to the human resources for health crisis in Africa. However, little attention has been paid to quantifying health facility-level trends in health worker numbers, distribution and workload, despite growing demands on health workers due to the availability of new funds for HIV/AIDS control scale-up. This study analyses and reports trends in HIV and non-HIV ambulatory service workloads on clinical staff in urban and rural district level facilities. Methods Structured surveys of health facility managers, and health services covering 2005-07 were conducted in three districts of Zambia in 2008 (two urban and one rural, to fill this evidence gap. Intra-facility analyses were conducted, comparing trends in HIV and non-HIV service utilisation with staff trends. Results Clinical staff (doctors, nurses and nurse-midwives, and clinical officers numbers and staff population densities fell slightly, with lower ratios of staff to population in the rural district. The ratios of antenatal care and family planning registrants to nurses/nurse-midwives were highest at baseline and increased further at the rural facilities over the three years, while daily outpatient department (OPD workload in urban facilities fell below that in rural facilities. HIV workload, as measured by numbers of clients receiving antiretroviral treatment (ART and prevention of mother to child transmission (PMTCT per facility staff member, was highest in the capital city, but increased rapidly in all three districts. The analysis suggests evidence of task sharing, in that staff designated by managers as ART and PMTCT workers made up a higher proportion of frontline service providers by 2007. Conclusions This analysis of workforce patterns across 30 facilities in three districts of Zambia illustrates that the remarkable achievements in scaling-up HIV/AIDS service delivery has been on the back of

  16. Developmental parallelism in primates.

    Science.gov (United States)

    Sikorska-Piwowska, Z M; Dawidowicz, A L

    2017-01-01

    The authors examined a large random sample of skulls from two species of macaques: rhesus monkeys and cynomolgus monkeys. The skulls were measured, divided into age and sex groups and thoroughly analysed using statistical methods. The analysis shows that skulls of young rhesuses are considerably more domed, i.e. have better-developed neurocrania, than their adult counterparts. Male and female skulls, on the other hand, were found to be very similar, which means that sexual dimorphism of the rhesus macaque was suppressed. Both of these patterns are known from the human evolutionary pattern. No such parallelism to the development of Homo sapiens was found in the cynomolgus monkeys. The authors conclude that mosaic hominisation trends may have featured in the evolution of all primates. This would mean that apes were not a necessary step on the evolutionary way leading to the development of Homo sapiens, who may have started to evolve at an earlier stage of monkeys.

  17. Ethics of primate use

    Science.gov (United States)

    Prescott, M. J.

    2010-11-01

    This article provides an overview of the ethical issues raised by the use of non-human primates (NHPs) in research involving scientific procedures which may cause pain, suffering, distress or lasting harm. It is not an exhaustive review of the literature and views on this subject, and it does not present any conclusions about the moral acceptability or otherwise of NHP research. Rather the aim has been to identify the ethical issues involved and to provide guidance on how these might be addressed, in particular by carefully examining the scientific rationale for NHP use, implementing fully the 3Rs principle of Russell and Burch (1959) and applying a robust "harm-benefit assessment" to research proposals involving NHPs.

  18. Methadone Maintenance Therapy in Vietnam: An Overview and Scaling-Up Plan

    Directory of Open Access Journals (Sweden)

    Tam T. M. Nguyen

    2012-01-01

    Full Text Available Vietnam is among the countries with the highest rate of HIV transmission through injecting drug users. HIV prevalence among injecting drug users is 20% and up to 50% in many provinces. An estimated number of drug users in the country by the end of 2011 were 171,000 in which the most common is heroin (85%. Detoxification at home, community, and in rehabilitation centers have been the main modalities for managing heroin addiction until Methadone Maintenance Treatment (MMT was piloted in 2008. Recent reports have demonstrated positive treatment outcomes. Incidence of HIV was found remarkably low among patients on MMT. Treatment has significantly improved the quality of life as well as stability for society. The government has granted the Ministry of Health (MoH to expand Methadone treatment to at least 30 provinces to provide treatment for more than 80,000 drug users by 2015. The Vietnam Administration for HIV/AIDS Control (VAAC and MOH have outlined the role and responsibility of key departments at the central and local levels in implementing and maintaining MMT treatment. This paper will describe the achievements of the MMT pilot program and the scaling-up plan as well as strategies to ensure quality and sustainability and to overcome the challenges in the coming years.

  19. Optimisation of rosemary oil encapsulation in polycaprolactone and scale-up of the process.

    Science.gov (United States)

    Ephrem, Elissa; Greige-Gerges, Hélène; Fessi, Hatem; Charcosset, Catherine

    2014-01-01

    Rosemary essential oil (REO) has many biological activities, such as antioxidant, anticarcinogenic, cognition-enhancing, analgesic and antimicrobial activities. The aim of this study was to prepare, at laboratory scale and larger scale, nanoencapsulating REO in order to reduce its volatilisation, light sensitivity and to enhance its water solubility. The nanoprecipitation method was applied to prepare polycaprolactone (PCL)-based nanocapsules loaded with REO at laboratory scale and then the optimal formulation obtained was scaled-up (×6) using the membrane contactor technique. The effect of several parameters, such as the evaporation method, the type of emulsifiers and the amount of the formulation products (PCL, REO, emulsifiers, etc.) on the REO-loaded nanocapsules properties (mean size, polydispersity index (PdI), zeta potential and REO loss) was evaluated at laboratory scale in order to obtain the optimal formulation. REO-loaded nanocapsules obtained from nanoprecipitation presented a nanometric mean size (220 ± 10 nm) with a PdI below 0.25, indicating an adequate homogeneity of the system, a negative zeta potential (-19.9 ± 4.6 mV) and a high encapsulation efficiency (∼99% for the major components). In addition, the membrane contactor technique gave similar results using an adequate pressure of the organic phase (0.8-1.2 bar). It is then suggested that the nanoprecipitation method can be suitable for the preparation of essential oil-loaded nanocapsules.

  20. Scaling up the Fabrication of Mechanically-Robust Carbon Nanofiber Foams

    Directory of Open Access Journals (Sweden)

    William Curtin

    2016-02-01

    Full Text Available This work aimed to identify and address the main challenges associated with fabricating large samples of carbon foams composed of interwoven networks of carbon nanofibers. Solutions to two difficulties related with the process of fabricating carbon foams, maximum foam size and catalyst cost, were developed. First, a simple physical method was invented to scale-up the constrained formation of fibrous nanostructures process (CoFFiN to fabricate relatively large foams. Specifically, a gas deflector system capable of maintaining conditions supportive of carbon nanofiber foam growth throughout a relatively large mold was developed. ANSYS CFX models were used to simulate the gas flow paths with and without deflectors; the data generated proved to be a very useful tool for the deflector design. Second, a simple method for selectively leaching the Pd catalyst material trapped in the foam during growth was successfully tested. Multiple techniques, including scanning electron microscopy, surface area measurements, and mechanical testing, were employed to characterize the foams generated in this study. All results confirmed that the larger foam samples preserve the basic characteristics: their interwoven nanofiber microstructure forms a low-density tridimensional solid with viscoelastic behavior. Fiber growth mechanisms are also discussed. Larger samples of mechanically-robust carbon nanofiber foams will enable the use of these materials as strain sensors, shock absorbers, selective absorbents for environmental remediation and electrodes for energy storage devices, among other applications.

  1. Methadone maintenance therapy in Vietnam: an overview and scaling-up plan.

    Science.gov (United States)

    Nguyen, Tam T M; Nguyen, Long T; Pham, Manh D; Vu, Hoang H; Mulvey, Kevin P

    2012-01-01

    Vietnam is among the countries with the highest rate of HIV transmission through injecting drug users. HIV prevalence among injecting drug users is 20% and up to 50% in many provinces. An estimated number of drug users in the country by the end of 2011 were 171,000 in which the most common is heroin (85%). Detoxification at home, community, and in rehabilitation centers have been the main modalities for managing heroin addiction until Methadone Maintenance Treatment (MMT) was piloted in 2008. Recent reports have demonstrated positive treatment outcomes. Incidence of HIV was found remarkably low among patients on MMT. Treatment has significantly improved the quality of life as well as stability for society. The government has granted the Ministry of Health (MoH) to expand Methadone treatment to at least 30 provinces to provide treatment for more than 80,000 drug users by 2015. The Vietnam Administration for HIV/AIDS Control (VAAC) and MOH have outlined the role and responsibility of key departments at the central and local levels in implementing and maintaining MMT treatment. This paper will describe the achievements of the MMT pilot program and the scaling-up plan as well as strategies to ensure quality and sustainability and to overcome the challenges in the coming years.

  2. The furthest left behind: the urgent need to scale up harm reduction in prisons.

    Science.gov (United States)

    Sander, Gen; Murphy, Fionnuala

    2017-09-11

    Purpose Raise awareness about the disproportionate impact of HIV and hepatitis C (HCV) on prisoners worldwide and the need for key harm reduction services such as needle and syringe programmes and opioid substitution therapy in prisons offer practical recommendations to assist policy makers in implementing or scaling up these services. The paper aims to discuss these issues. Design/methodology/approach This study is a desk review of existing data and evidence on HIV, HCV and harm reduction in prisons, analysis of political barriers and formulation of key policy recommendations. Findings Harm reduction works, yet service provision in prisons remains extremely limited. There is an urgent need for governments to enhance political leadership and funding for harm reduction in prisons. Authorities must also work to remove obstacles to the implementation of harm reduction services in prisons, enhance the monitoring and evaluation of laws, policies and programmes relating to HIV, HCV and drugs in prison settings, and recognise access to harm reduction in prisons as a fundamental human right. Until these obstacles are addressed, the world will not meet the Sustainable Development Goal of eradicating HIV and HCV by 2030. Originality/value More than just a desk review, this policy brief provides a political analysis of the harm reduction crisis in prisons and offers clear-cut recommendations for policy makers.

  3. Scaling up high throughput field phenotyping of corn and soy research plots using ground rovers

    Science.gov (United States)

    Peshlov, Boyan; Nakarmi, Akash; Baldwin, Steven; Essner, Scott; French, Jasenka

    2017-05-01

    Crop improvement programs require large and meticulous selection processes that effectively and accurately collect and analyze data to generate quality plant products as efficiently as possible, develop superior cropping and/or crop improvement methods. Typically, data collection for such testing is performed by field teams using hand-held instruments or manually-controlled devices. Although steps are taken to reduce error, the data collected in such manner can be unreliable due to human error and fatigue, which reduces the ability to make accurate selection decisions. Monsanto engineering teams have developed a high-clearance mobile platform (Rover) as a step towards high throughput and high accuracy phenotyping at an industrial scale. The rovers are equipped with GPS navigation, multiple cameras and sensors and on-board computers to acquire data and compute plant vigor metrics per plot. The supporting IT systems enable automatic path planning, plot identification, image and point cloud data QA/QC and near real-time analysis where results are streamed to enterprise databases for additional statistical analysis and product advancement decisions. Since the rover program was launched in North America in 2013, the number of research plots we can analyze in a growing season has expanded dramatically. This work describes some of the successes and challenges in scaling up of the rover platform for automated phenotyping to enable science at scale.

  4. Engineering integrated digital circuits with allosteric ribozymes for scaling up molecular computation and diagnostics.

    Science.gov (United States)

    Penchovsky, Robert

    2012-10-19

    Here we describe molecular implementations of integrated digital circuits, including a three-input AND logic gate, a two-input multiplexer, and 1-to-2 decoder using allosteric ribozymes. Furthermore, we demonstrate a multiplexer-decoder circuit. The ribozymes are designed to seek-and-destroy specific RNAs with a certain length by a fully computerized procedure. The algorithm can accurately predict one base substitution that alters the ribozyme's logic function. The ability to sense the length of RNA molecules enables single ribozymes to be used as platforms for multiple interactions. These ribozymes can work as integrated circuits with the functionality of up to five logic gates. The ribozyme design is universal since the allosteric and substrate domains can be altered to sense different RNAs. In addition, the ribozymes can specifically cleave RNA molecules with triplet-repeat expansions observed in genetic disorders such as oculopharyngeal muscular dystrophy. Therefore, the designer ribozymes can be employed for scaling up computing and diagnostic networks in the fields of molecular computing and diagnostics and RNA synthetic biology.

  5. Fortification of condiments with micronutrients in public health: from proof of concept to scaling up.

    Science.gov (United States)

    Garcia-Casal, Maria Nieves; Peña-Rosas, Juan Pablo; Mclean, Mireille; De-Regil, Luz María; Zamora, Gerardo

    2016-09-01

    Fortification of condiments or seasonings may be useful for delivering micronutrients if they are consumed consistently by most of the population, as occurs in many countries. The World Health Organization, in collaboration with the Micronutrient Initiative and the Sackler Institute for Nutrition Science at the New York Academy of Sciences, convened a technical consultation on "Fortification of Condiments and Seasonings with Vitamins and Minerals in Public Health: from Proof of Concept to Scaling Up" to review the role of condiments and seasonings in improving micronutrient status, as constituents of regular diets and patterns of production and consumption worldwide. The consultation covered aspects related to implementation, monitoring, evaluation, and legal frameworks of fortification programs, as well as food safety and policy coherence for condiment fortification in the context of other public health strategies. This paper introduces the background and rationale of the technical consultation, synopsizes the presentations, and provides a summary of the main considerations proposed by the working groups. © 2016 New York Academy of Sciences.

  6. Scale-up potential of cultivating Chlorella zofingiensis in piggery wastewater for biodiesel production.

    Science.gov (United States)

    Yuan, Zhenhong; Wang, Zhongming; Takala, Josu; Hiltunen, Erkki; Qin, Lei; Xu, Zhongbin; Qin, Xiaoxi; Zhu, Liandong

    2013-06-01

    Scale-up potential of cultivating Chlorella zofingiensis in piggery wastewater for simultaneous wastewater treatment and biodiesel production was tested. The cultivation of C. zofingiensis with autoclaved wastewater and NaClO-pretreated wastewater, cultivation of algae indoors and outdoors, and stability of semi-continuous feeding operation were examined. The results showed that C. zofingiensis cultivated in piggery wastewater pretreated by autoclaving and NaClO had no evident difference in the performance of nutrient removal, algal growth and biodiesel production. The outdoor cultivation experiments indicated that C. zofingiensis was able to adapt and grow well outdoors. The semi-continuous feeding operation by replacing 50% of algae culture with fresh wastewater every 1.5 days could provide a stable net biomass productivity of 1.314 g L(-1) day(-1). These findings in this study can prove that it is greatly possible to amplify the cultivation of C. zofingiensis in piggery wastewater for nutrient removal and biodiesel production. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Batch fermentation of black tea by kombucha: A contribution to scale-up

    Directory of Open Access Journals (Sweden)

    Malbaša Radomir V.

    2005-01-01

    Full Text Available Local domestic Kombucha was used in fermentation of 1.5 g L-1 of black tea (Indian tea, " Vitamin ", Horgoš, Serbia and Montenegro, sweetened with approximately 70 g L'1 of sucrose. Inoculation was performed either with 10% or 15% (v/v of fermentation broth from previous process. The fermentation was conducted in geometrically similar vessels with 0.4 L, 0.8 L, 4 L and 8 L of substrate, at 22±1 °C for 28 days. The samples were analyzed after 3, 4 5, 6, 7, 10, 14 and 28 days, so that their pH values, content of total acids sucrose, glucose and fructose contents, as well as contents of ethanol and vitamin C were determined. Based on the experiment design, the response surface for the product pH, as a function of time, beverage volume and inoculum concentration, was defined in the form of a second-order polynomial. From the obtained response surface, a formula for scaling-up of the process was derived.

  8. Development of biomimetic system for scale up of cell spheroids - building blocks for cell transplantation.

    Science.gov (United States)

    Baba, Kazutomo; Sankai, Yoshiyuki

    2017-07-01

    Artificial assembly of mature tissues in vitro is challenging from many viewpoints. Therefore, production of intermediate building blocks - cell spheroids expected to be a viable alternative. The purpose of this research is to develop a biomimetic system for scale up maintenance of spheroids in vitro, and to confirm basic performance of the device. The system consists of a 3D culture unit and a medium perfusion unit. The 3D culture unit is dedicated for spheroid culture without using scaffolds, eliminating concerns about biocompatibility of artificial materials. our culture vessel allows easy disassembly and tissue extraction, as well as the resulting tissue can be formed into an any desirable shape. The spheroids are cultured in a sealed environment and their life are sustained by hollow fiber perfusion fluidics. We confirmed by visual and by microscopic examination that no contamination did occur before and after spheroid inoculation. Moreover, we confirmed growth and fusion between cells when C2C12 spheroids were cultured in this system.

  9. Scaling up antiretroviral therapy in resource-limited settings: adapting guidance to meet the challenges.

    Science.gov (United States)

    Vitoria, Marco; Vella, Stefano; Ford, Nathan

    2013-01-01

    This review describes the evolution of WHO guidelines for antiretroviral therapy (ART) in HIV-infected individuals, considering the key epidemiological, scientific, programmatic, and political changes over the last decade, and highlights the major trends for the management of the HIV disease in future guidelines revisions. In the last few years, new evidence has emerged supporting the potential preventive benefit of ART in reducing HIV transmission. This, together with the potential clinical benefits of earlier initiation of therapy, has led to the consideration of the broader strategic use of ART, taking into account the clinical and public health benefit, and programmatic feasibility. In 2002, WHO established its first guidelines for ART use, primarily focused on a public health approach for resource-limited settings. These recommendations were updated in 2003, 2006, and 2010, incorporating progressive changes reflecting progressive increase in the knowledge of HIV pathogenesis, development of new drugs and diagnostics, and increased experience of HIV treatment and prevention programs. The impact of several international political commitments and scale-up initiatives such as the 3 by 5 Initiative, Universal Access targets, and the Treatment 2.0 Strategy were also important drivers of the global response, increasing the treatment coverage and catalyzing the necessary environment for the establishment of operational and programmatic components for an expanded and sustainable global response to HIV/AIDS.

  10. Nb3Sn accelerator magnet technology scale up using cos-theta dipole coils

    Energy Technology Data Exchange (ETDEWEB)

    Nobrega, F.; Andreev, N.; Ambrosio, G.; Barzi, E.; Bossert, R.; Carcagno, R.; Chlachidze, G.; Feher, S.; Kashikhin, V.S.; Kashikhin, V.V.; Lamm, M.J.; /Fermilab

    2007-06-01

    Fermilab is working on the development of Nb{sub 3}Sn accelerator magnets using shell-type dipole coils and the wind-and-react method. As a part of the first phase of technology development, Fermilab built and tested six 1 m long dipole model magnets and several dipole mirror configurations. The last three dipoles and two mirrors reached their design fields of 10-11 T. The technology scale up phase has started by building 2 m and 4 m dipole coils and testing them in a mirror configuration in which one of the two coils is replaced by a half-cylinder made of low carbon steel. This approach allows for shorter fabrication times and extensive instrumentation preserving almost the same level of magnetic field and Lorentz forces in the coils as in a complete dipole model magnet. This paper presents details on the 2 m (HFDM07) and 4 m long (HFDM08) Nb{sub 3}Sn dipole mirror magnet design and fabrication technology, as well as the magnet test results which are compared with 1 m long models.

  11. Design of an 80 kWe PEM fuel cell system: Scale up effect investigation

    Energy Technology Data Exchange (ETDEWEB)

    Bonnet, C.; Carre, P. [Laboratoire des Sciences du Genie Chimique, Nancy-University-CNRS, 1 rue Grandville, BP20451, 54001 Nancy (France); Didierjean, S.; Colinart, T. [Laboratoire d' Energetique et de Mecanique Theorique et Appliquee, Nancy-University-CNRS, 2 avenue de la Foret de Haye, 54504 Vandoeuvre les Nancy (France); Guillet, N. [CEA-Grenoble LITEN/DTH/LCPEM, 17, rue des martyrs, 38054 Grenoble Cedex 9 (France); Besse, S. [Helion, Domaine du Petit Arbois, Batiment Jules Verne, BP71, 13545 Aix en Provence Cedex 4 (France)

    2008-08-01

    In the frame of SPACT-80 project to design and manufacture a robust and durable air/hydrogen 80 kWe PEM fuel cell for transportation application, experiments have been carried out on various electrode active surfaces since the full scale system could be damaged by some particular operating conditions. Thus, the main objective of this paper was to verify that a 25 cm{sup 2} single cell, a 5-cell pilot stack and a 90-cell stack exhibit the same behaviour and that they are representative of the full device's performance. After a brief description of the studied device the scaling up effect was checked. In non-optimal conditions, experiments were mainly conducted on single cell and pilot stack. In driving cycle and when studying various gas flows, they present similar evolution for the cell voltage as well as for the water management. The water transport coefficient and the diffusion resistance values determined by impedance spectroscopy highlight the presence of liquid water that could have an effect on the gas transport to the electrode. Investigation on the air humidification conditions shows that at lower relative humidity (RH), the two fuel cells have similar behaviour but above 60% RH different evolutions appear. Whatever the air humidification conditions, liquid water is present in both compartments. (author)

  12. Context matters: Successes and challenges of intrapartum care scale-up in four districts of Afghanistan.

    Science.gov (United States)

    Tappis, Hannah; Koblinsky, Marge; Winch, Peter J; Turkmani, Sabera; Bartlett, Linda

    2016-01-01

    Reducing preventable maternal mortality and achieving Sustainable Development Goal targets for 2030 will require increased investment in improving access to quality health services in fragile and conflict-affected states. This study explores the conditions that affect availability and utilisation of intrapartum care services in four districts of Afghanistan where mortality studies were conducted in 2002 and 2011. Information on changes in each district was collected through interviews with community members; service providers; and district, provincial and national officials. This information was then triangulated with programme and policy documentation to identify factors that affect the coverage of safe delivery and emergency obstetric care services. Comparison of barriers to maternal health service coverage across the four districts highlights the complexities of national health policy planning and resource allocation in Afghanistan, and provides examples of the types of challenges that must be addressed to extend the reach of life-saving maternal health interventions to women in fragile and conflict-affected states. Findings suggest that improvements in service coverage must be measured at a sub-national level, and context-specific service delivery models may be needed to effectively scale up intrapartum care services in extremely remote or insecure settings.

  13. Fan-out Estimation in Spin-based Quantum Computer Scale-up.

    Science.gov (United States)

    Nguyen, Thien; Hill, Charles D; Hollenberg, Lloyd C L; James, Matthew R

    2017-10-17

    Solid-state spin-based qubits offer good prospects for scaling based on their long coherence times and nexus to large-scale electronic scale-up technologies. However, high-threshold quantum error correction requires a two-dimensional qubit array operating in parallel, posing significant challenges in fabrication and control. While architectures incorporating distributed quantum control meet this challenge head-on, most designs rely on individual control and readout of all qubits with high gate densities. We analysed the fan-out routing overhead of a dedicated control line architecture, basing the analysis on a generalised solid-state spin qubit platform parameterised to encompass Coulomb confined (e.g. donor based spin qubits) or electrostatically confined (e.g. quantum dot based spin qubits) implementations. The spatial scalability under this model is estimated using standard electronic routing methods and present-day fabrication constraints. Based on reasonable assumptions for qubit control and readout we estimate 102-105 physical qubits, depending on the quantum interconnect implementation, can be integrated and fanned-out independently. Assuming relatively long control-free interconnects the scalability can be extended. Ultimately, the universal quantum computation may necessitate a much higher number of integrated qubits, indicating that higher dimensional electronics fabrication and/or multiplexed distributed control and readout schemes may be the preferredstrategy for large-scale implementation.

  14. Polyethylene encapsulatin of nitrate salt wastes: Waste form stability, process scale-up, and economics

    Energy Technology Data Exchange (ETDEWEB)

    Kalb, P.D.; Heiser, J.H. III; Colombo, P.

    1991-07-01

    A polyethylene encapsulation system for treatment of low-level radioactive, hazardous, and mixed wastes has been developed at Brookhaven National Laboratory. Polyethylene has several advantages compared with conventional solidification/stabilization materials such as hydraulic cements. Waste can be encapsulated with greater efficiency and with better waste form performance than is possible with hydraulic cement. The properties of polyethylene relevant to its long-term durability in storage and disposal environments are reviewed. Response to specific potential failure mechanisms including biodegradation, radiation, chemical attack, flammability, environmental stress cracking, and photodegradation are examined. These data are supported by results from extensive waste form performance testing including compressive yield strength, water immersion, thermal cycling, leachability of radioactive and hazardous species, irradiation, biodegradation, and flammability. The bench-scale process has been successfully tested for application with a number of specific problem'' waste streams. Quality assurance and performance testing of the resulting waste form confirmed scale-up feasibility. Use of this system at Rocky Flats Plant can result in over 70% fewer drums processed and shipped for disposal, compared with optimal cement formulations. Based on the current Rocky Flats production of nitrate salt per year, polyethylene encapsulation can yield an estimated annual savings between $1.5 million and $2.7 million, compared with conventional hydraulic cement systems. 72 refs., 23 figs., 16 tabs.

  15. Scaling-up permafrost thermal measurements in western Alaska using an ecotype approach

    Directory of Open Access Journals (Sweden)

    W. L. Cable

    2016-10-01

    Full Text Available Permafrost temperatures are increasing in Alaska due to climate change and in some cases permafrost is thawing and degrading. In areas where degradation has already occurred the effects can be dramatic, resulting in changing ecosystems, carbon release, and damage to infrastructure. However, in many areas we lack baseline data, such as subsurface temperatures, needed to assess future changes and potential risk areas. Besides climate, the physical properties of the vegetation cover and subsurface material have a major influence on the thermal state of permafrost. These properties are often directly related to the type of ecosystem overlaying permafrost. In this paper we demonstrate that classifying the landscape into general ecotypes is an effective way to scale up permafrost thermal data collected from field monitoring sites. Additionally, we find that within some ecotypes the absence of a moss layer is indicative of the absence of near-surface permafrost. As a proof of concept, we used the ground temperature data collected from the field sites to recode an ecotype land cover map into a map of mean annual ground temperature ranges at 1 m depth based on analysis and clustering of observed thermal regimes. The map should be useful for decision making with respect to land use and understanding how the landscape might change under future climate scenarios.

  16. Vaccinium meridionale Swartz Supercritical CO2 Extraction: Effect of Process Conditions and Scaling Up

    Directory of Open Access Journals (Sweden)

    Alexis López-Padilla

    2016-06-01

    Full Text Available Vaccinium meridionale Swartz (Mortiño or Colombian blueberry is one of the Vaccinium species abundantly found across the Colombian mountains, which are characterized by high contents of polyphenolic compounds (anthocyanins and flavonoids. The supercritical fluid extraction (SFE of Vaccinium species has mainly focused on the study of V. myrtillus L. (blueberry. In this work, the SFE of Mortiño fruit from Colombia was studied in a small-scale extraction cell (273 cm3 and different extraction pressures (20 and 30 MPa and temperatures (313 and 343 K were investigated. Then, process scaling-up to a larger extraction cell (1350 cm3 was analyzed using well-known semi-empirical engineering approaches. The Broken and Intact Cell (BIC model was adjusted to represent the kinetic behavior of the low-scale extraction and to simulate the large-scale conditions. Extraction yields obtained were in the range 0.1%–3.2%. Most of the Mortiño solutes are readily accessible and, thus, 92% of the extractable material was recovered in around 30 min. The constant CO2 residence time criterion produced excellent results regarding the small-scale kinetic curve according to the BIC model, and this conclusion was experimentally validated in large-scale kinetic experiments.

  17. Production of drug metabolites by immobilised Cunninghamella elegans: from screening to scale up.

    Science.gov (United States)

    Quinn, Laura; Dempsey, Rita; Casey, Eoin; Kane, Ayla; Murphy, Cormac D

    2015-05-01

    Cunninghamella elegans is a fungus that has been used extensively as a microbial model of mammalian drug metabolism, whilst its potential as a biocatalyst for the preparative production of human drug metabolites has been often proposed, little effort has been made to enable this. Here, we describe a workflow for the application of C. elegans for the production of drug metabolites, starting from well-plate screening assays leading to the preparative production of drug metabolites using fungus immobilised either in alginate or as a biofilm. Using 12- and 96-well plates, the simultaneous screening of several drug biotransformations was achieved. To scale up the biotransformation, both modes of immobilisation enabled semi-continuous production of hydroxylated drug metabolites through repeated addition of drug and rejuvenation of the fungus. It was possible to improve the productivity in the biofilm culture for the production of 4'-hydroxydiclofenac from 1 mg/l h to over 4 mg/l h by reducing the incubation time for biotransformation and the number of rejuvenation steps.

  18. Water based scale-up of CPO-27 synthesis for nitric oxide delivery.

    Science.gov (United States)

    Cattaneo, Damiano; Warrender, Stewart J; Duncan, Morven J; Castledine, Richard; Parkinson, Nigel; Haley, Ian; Morris, Russell E

    2016-01-14

    The applicability of water-based reflux and room temperature synthesis processes for the production of CPO-27 MOFs, suitable for NO delivery applications, is investigated. NO adsorption, storage and release performance of products obtained under reflux conditions are comparable to those of equivalent samples synthesised from traditional solvothermal methods at small scale. Products obtained from room temperature processes show lower NO release capability, although the quantities that are released are still more than adequate for biomedical applications. Results also reveal differences for the first time in NO uptake, storage and release depending on whether Zn, Ni or Mg is employed. The results indicate that while the crystallinity of CPO-27(Zn) and CPO-27(Mg) is not affected by moving to lower temperature methods, the crystallinity of CPO-27(Ni) is reduced. Particle morphology and size is also affected. The low temperature processes are successfully demonstrated at 20 L and 100 L scale and the main problems encountered during scale-up are outlined. The 100 L scale is in itself an appropriate production scale for some niche biomedical products. Indeed, results indicate that this synthesis approach is suitable for commercial production of MOFs for this application field. We also confirm that BET surface area from nitrogen adsorption at 77 K is not a good indicator for successful adsorption of NO.

  19. Transforming Global Health by Improving the Science of Scale-Up.

    Directory of Open Access Journals (Sweden)

    Margaret E Kruk

    2016-03-01

    Full Text Available In its report Global Health 2035, the Commission on Investing in Health proposed that health investments can reduce mortality in nearly all low- and middle-income countries to very low levels, thereby averting 10 million deaths per year from 2035 onward. Many of these gains could be achieved through scale-up of existing technologies and health services. A key instrument to close this gap is policy and implementation research (PIR that aims to produce generalizable evidence on what works to implement successful interventions at scale. Rigorously designed PIR promotes global learning and local accountability. Much greater national and global investments in PIR capacity will be required to enable the scaling of effective approaches and to prevent the recycling of failed ideas. Sample questions for the PIR research agenda include how to close the gap in the delivery of essential services to the poor, which population interventions for non-communicable diseases are most applicable in different contexts, and how to engage non-state actors in equitable provision of health services in the context of universal health coverage.

  20. Scale-up of phosphate remobilization from sewage sludge in a microbial fuel cell.

    Science.gov (United States)

    Happe, Manuel; Sugnaux, Marc; Cachelin, Christian Pierre; Stauffer, Marc; Zufferey, Géraldine; Kahoun, Thomas; Salamin, Paul-André; Egli, Thomas; Comninellis, Christos; Grogg, Alain-François; Fischer, Fabian

    2016-01-01

    Phosphate remobilization from digested sewage sludge containing iron phosphate was scaled-up in a microbial fuel cell (MFC). A 3litre triple chambered MFC was constructed. This reactor was operated as a microbial fuel cell and later as a microbial electrolysis cell to accelerate cathodic phosphate remobilization. Applying an additional voltage and exceeding native MFC power accelerated chemical base formation and the related phosphate remobilization rate. The electrolysis approach was extended using a platinum-RVC cathode. The pH rose to 12.6 and phosphate was recovered by 67% in 26h. This was significantly faster than using microbial fuel cell conditions. Shrinking core modelling particle fluid kinetics showed that the reaction resistance has to move inside the sewage sludge particle for considerable rate enhancement. Remobilized phosphate was subsequently precipitated as struvite and inductively coupled plasma mass spectrometry indicated low levels of cadmium, lead, and other metals as required by law for recycling fertilizers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Multiphase flow modeling: A tool to aid in scale up of processes

    Science.gov (United States)

    Nandakumar, Krishnaswamy

    2010-10-01

    Multiphase flows are ubiquitous in chemical processing industries. Traditional approach has been to ignore fluid dynamical effects by invoking simplifying assumptions of homogeneity, but pay the price during scale-up of processes. The question that I address is ``Can Multiphase flow modeling come to our rescue in minimizing the need for pilot scale experiments?'' On the fundamental side, we have developed algorithms for direct numerical simulation of multiphase flows. For dispersed rigid particles as in suspension flows, sedimentation etc, we couple the Navier-Stokes equations with the rigid body dynamics in a rigorous fashion to track the particle motion in a fluid. For deformable bubbles/droplets dispersed in another fluid, we also track their motion in an Eulerian grid. The two classes of algorithms show great promise in attempting direct simulation of multiphase flows, from which we can extract statistically meaningful average behavior of suspensions or bubbly flows. On the other hand, there is an immediate need to study flow of complex fluids of industrial importance. Such cases include polymer blending processes, erosion in pipelines and process vessels and mass transfer in packed beds. In such studies we use volume averaged equations as the basis of flow models coupled with experimental validation of such predictions in an effort to develop scale invariant closure models that are needed as part of the volume averaged flow models.

  2. Scale-up of a Luminescent Solar Concentrator-Based Photomicroreactor via Numbering-up

    Science.gov (United States)

    2017-01-01

    The use of solar energy to power chemical reactions is a long-standing dream of the chemical community. Recently, visible-light-mediated photoredox catalysis has been recognized as the ideal catalytic transformation to convert solar energy into chemical bonds. However, scaling photochemical transformations has been extremely challenging due to Bouguer–Lambert–Beer law. Recently, we have pioneered the development of luminescent solar concentrator photomicroreactors (LSC-PMs), which display an excellent energy efficiency. These devices harvest solar energy, convert the broad solar energy spectrum to a narrow-wavelength region, and subsequently waveguide the re-emitted photons to the reaction channels. Herein, we report on the scalability of such LSC-PMs via a numbering-up strategy. Paramount in our work was the use of molds that were fabricated via 3D printing. This allowed us to rapidly produce many different prototypes and to optimize experimentally key design aspects in a time-efficient fashion. Reactors up to 32 parallel channels have been fabricated that display an excellent flow distribution using a bifurcated flow distributor (standard deviations below 10%). This excellent flow distribution was crucial to scale up a model reaction efficiently, displaying yields comparable to those obtained in a single-channel device. We also found that interchannel spacing is an important and unique design parameter for numbered-up LSC-PMs, which influences greatly the photon flux experienced within the reaction channels. PMID:29333350

  3. Scaling-up permafrost thermal measurements in western Alaska using an ecotype approach

    Science.gov (United States)

    Cable, William L.; Romanovsky, Vladimir E.; Torre Jorgenson, M.

    2016-10-01

    Permafrost temperatures are increasing in Alaska due to climate change and in some cases permafrost is thawing and degrading. In areas where degradation has already occurred the effects can be dramatic, resulting in changing ecosystems, carbon release, and damage to infrastructure. However, in many areas we lack baseline data, such as subsurface temperatures, needed to assess future changes and potential risk areas. Besides climate, the physical properties of the vegetation cover and subsurface material have a major influence on the thermal state of permafrost. These properties are often directly related to the type of ecosystem overlaying permafrost. In this paper we demonstrate that classifying the landscape into general ecotypes is an effective way to scale up permafrost thermal data collected from field monitoring sites. Additionally, we find that within some ecotypes the absence of a moss layer is indicative of the absence of near-surface permafrost. As a proof of concept, we used the ground temperature data collected from the field sites to recode an ecotype land cover map into a map of mean annual ground temperature ranges at 1 m depth based on analysis and clustering of observed thermal regimes. The map should be useful for decision making with respect to land use and understanding how the landscape might change under future climate scenarios.

  4. PEPFAR Support for the Scaling Up of Collaborative TB/HIV Activities

    Science.gov (United States)

    Howard, Andrea A.; Gasana, Michel; Getahun, Haileyesus; Harries, Anthony; Lawn, Stephen D.; Miller, Bess; Nelson, Lisa; Sitienei, Joseph; Coggin, William L.

    2014-01-01

    The US President’s Emergency Plan for AIDS Relief (PEPFAR) has supported a comprehensive package of care in which interventions to address HIV-related tuberculosis (TB) have received increased funding and support in recent years. PEPFAR’s TB/HIV programming is based on the World Health Organization 12-point policy for collaborative TB/HIV activities, which are integrated into PEPFAR annual guidance. PEPFAR implementing partners have provided crucial support to TB/HIV collaboration, and as a result PEPFAR-supported countries in sub-Saharan Africa have made significant gains in HIV testing and counseling of TB patients and linkages to HIV care and treatment, intensified TB case finding, and TB infection control. PEPFAR’s support of TB/HIV integration has also included significant investment in health systems, including improved laboratory services and educating and enlarging the workforce. The scale-up of antiretroviral therapy along with support of programs to increase HIV counseling and testing and improve linkage and retention in HIV care may have considerable impact on TB morbidity and mortality, if used synergistically with isoniazid preventive therapy (IPT), intensified case finding and infection control. Issues to be addressed by future programming include accelerating implementation of IPT, increasing access and ensuring appropriate use of new TB diagnostics, supporting early initiation of antiretroviral therapy for HIV-infected TB patients, and strengthening systems to monitor and evaluate program implementation. PMID:22797735

  5. Simulation for Supporting Scale-Up of a Fluidized Bed Reactor for Advanced Water Oxidation

    Science.gov (United States)

    Abdul Raman, Abdul Aziz; Daud, Wan Mohd Ashri Wan

    2014-01-01

    Simulation of fluidized bed reactor (FBR) was accomplished for treating wastewater using Fenton reaction, which is an advanced oxidation process (AOP). The simulation was performed to determine characteristics of FBR performance, concentration profile of the contaminants, and various prominent hydrodynamic properties (e.g., Reynolds number, velocity, and pressure) in the reactor. Simulation was implemented for 2.8 L working volume using hydrodynamic correlations, continuous equation, and simplified kinetic information for phenols degradation as a model. The simulation shows that, by using Fe3+ and Fe2+ mixtures as catalyst, TOC degradation up to 45% was achieved for contaminant range of 40–90 mg/L within 60 min. The concentration profiles and hydrodynamic characteristics were also generated. A subsequent scale-up study was also conducted using similitude method. The analysis shows that up to 10 L working volume, the models developed are applicable. The study proves that, using appropriate modeling and simulation, data can be predicted for designing and operating FBR for wastewater treatment. PMID:25309949

  6. Approaches to scaling up physiological responses of forests to air pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Luxmoore, R.J.

    1991-12-31

    The regional distribution of a forest specie encompasses favorable and unfavorable environments. Modeling of physiological responses of trees to air pollutants in such a range of environments requires a consistent level of modeling detail for both above- and below-ground processes. A source-sink framework is recommended as a suitable physiological basis for modeling the feed forward and feedback relationships between photosynthesis and carbon utilization of forest stands distributed over a heterogeneous region. The variability of soil and plant properties over a region can be represented with frequency distributions of model input variables and these can be efficiently propagated through a simulator with a Monte Carlo procedure called Latin hypercube sampling. The outputs from this method (e.g. forest production, site index) are in the form of frequency distributions that can be compared statistically for alternative air pollutant exposure scenarios. These outputs from physiological modeling can also be used as input distributions in longer time-step models of forest succession and forest management. Selection of suitable variables to propagate from one scale to another is a critical challenge in simulation of long-term forest responses to air pollutants over regional spatial scales. An index of storage carbohydrate is suggested as one important variable for transfer from physiological modeling to forest succession modeling for scaling up purposes.

  7. Optimisation of one-step desolvation and scale-up of gelatine nanoparticle production.

    Science.gov (United States)

    Geh, Katharina J; Hubert, Madlen; Winter, Gerhard

    2016-11-01

    Gelatine nanoparticles (GNPs) are biodegradable and biocompatible drug delivery systems with excellent clinical performances. A two-step desolvation is commonly used for their preparation, although this methodology has several shortcomings: lack of reproducibility, small scales and low yields. A straightforward and more consistent GNP preparation approach is presented here focusing on the development of a one-step desolvation with the use of a commercially available gelatine type. Controlled stirring conditions and ultrafiltration are used to achieve large-scale production of nanoparticles of up to 2.6 g per batch. Particle size distributions are conserved and comparable to those determined for two-step desolvation on small scale. Additionally, a range of cross-linking agents is examined for their effectiveness in stabilising GNPs as an alternative to glutaraldehyde. Glyceraldehyde demonstrated outstanding properties, which led to high colloidal stability. This approach optimises the manufacturing process and the scale-up of the production capacity, providing a clear potential for future applications.

  8. Vaccinium meridionale Swartz Supercritical CO2 Extraction: Effect of Process Conditions and Scaling Up

    Science.gov (United States)

    López-Padilla, Alexis; Ruiz-Rodriguez, Alejandro; Restrepo Flórez, Claudia Estela; Rivero Barrios, Diana Marsela; Reglero, Guillermo; Fornari, Tiziana

    2016-01-01

    Vaccinium meridionale Swartz (Mortiño or Colombian blueberry) is one of the Vaccinium species abundantly found across the Colombian mountains, which are characterized by high contents of polyphenolic compounds (anthocyanins and flavonoids). The supercritical fluid extraction (SFE) of Vaccinium species has mainly focused on the study of V. myrtillus L. (blueberry). In this work, the SFE of Mortiño fruit from Colombia was studied in a small-scale extraction cell (273 cm3) and different extraction pressures (20 and 30 MPa) and temperatures (313 and 343 K) were investigated. Then, process scaling-up to a larger extraction cell (1350 cm3) was analyzed using well-known semi-empirical engineering approaches. The Broken and Intact Cell (BIC) model was adjusted to represent the kinetic behavior of the low-scale extraction and to simulate the large-scale conditions. Extraction yields obtained were in the range 0.1%–3.2%. Most of the Mortiño solutes are readily accessible and, thus, 92% of the extractable material was recovered in around 30 min. The constant CO2 residence time criterion produced excellent results regarding the small-scale kinetic curve according to the BIC model, and this conclusion was experimentally validated in large-scale kinetic experiments. PMID:28773640

  9. Ammonia recovery from urine in a scaled-up Microbial Electrolysis Cell

    Science.gov (United States)

    Zamora, Patricia; Georgieva, Tanya; Ter Heijne, Annemiek; Sleutels, Tom H. J. A.; Jeremiasse, Adriaan W.; Saakes, Michel; Buisman, Cees J. N.; Kuntke, Philipp

    2017-07-01

    A two-step treatment system for nutrient and energy recovery from urine was successfully operated for six months. In the first step, phosphorus (P) was recovered as struvite (magnesium ammonium phosphate or MAP) in a MAP reactor. The effluent of this MAP reactor was used for total ammonia-nitrogen (TAN) recovery and hydrogen production in a Microbial Electrolysis Cell (MEC). This MEC was coupled to a Transmembranechemisorption (TMCS) module, in which the TAN was recovered as an ammonium sulphate solution. The MEC had a projected surface area of 0.5 m2 and was operated at different urine dilutions. The system was stable during the operation on 2 times diluted and undiluted urine at an applied voltage of 0.5 V with an average current density of 1.7 ± 0.2 A m-2. During stable current production, the TAN transport efficiency over the CEM was 92 ± 25% and the TAN recovery was 31 ± 59%. In terms of energy efficiency, the electrical energy required for the TAN recovery was 4.9 ± 1.0 MJ kgN-1, which is lower than competing electrochemical nitrogen removal/recovery technologies. Overall, this study shows, for the first time, the application of a scaled-up MEC for nutrient recovery from urine.

  10. Vaccinium meridionale Swartz Supercritical CO₂ Extraction: Effect of Process Conditions and Scaling Up.

    Science.gov (United States)

    López-Padilla, Alexis; Ruiz-Rodriguez, Alejandro; Restrepo Flórez, Claudia Estela; Rivero Barrios, Diana Marsela; Reglero, Guillermo; Fornari, Tiziana

    2016-06-25

    Vaccinium meridionale Swartz (Mortiño or Colombian blueberry) is one of the Vaccinium species abundantly found across the Colombian mountains, which are characterized by high contents of polyphenolic compounds (anthocyanins and flavonoids). The supercritical fluid extraction (SFE) of Vaccinium species has mainly focused on the study of V. myrtillus L. (blueberry). In this work, the SFE of Mortiño fruit from Colombia was studied in a small-scale extraction cell (273 cm³) and different extraction pressures (20 and 30 MPa) and temperatures (313 and 343 K) were investigated. Then, process scaling-up to a larger extraction cell (1350 cm³) was analyzed using well-known semi-empirical engineering approaches. The Broken and Intact Cell (BIC) model was adjusted to represent the kinetic behavior of the low-scale extraction and to simulate the large-scale conditions. Extraction yields obtained were in the range 0.1%-3.2%. Most of the Mortiño solutes are readily accessible and, thus, 92% of the extractable material was recovered in around 30 min. The constant CO₂ residence time criterion produced excellent results regarding the small-scale kinetic curve according to the BIC model, and this conclusion was experimentally validated in large-scale kinetic experiments.

  11. Scaling up access to oral rehydration solution for diarrhea: Learning from historical experience in low- and high-performing countries.

    Science.gov (United States)

    Wilson, Shelby E; Morris, Saul S; Gilbert, Sarah Skye; Mosites, Emily; Hackleman, Rob; Weum, Kristoffer L M; Pintye, Jillian; Manhart, Lisa E; Hawes, Stephen E

    2013-06-01

    This paper aims to identify factors that systematically predict why some countries that have tried to scale up oral rehydration solution (ORS) have succeeded, and others have not. We examined ORS coverage over time, across countries, and through case studies. We conducted expert interviews and literature and data searches to better understand the history of ORS scale-up efforts and why they failed or succeeded in nine countries. We used qualitative, pairwise (or three-country) comparisons of geographically or otherwise similar countries that had different outcomes in terms of ORS scale-up. An algorithm was developed which scored country performance across key supply, demand and financing activities to quantitatively assess the scale-up efforts in each country. The vast majority of countries have neither particularly low nor encouragingly high ORS use rates. We observed three clearly identifiable contrasts between countries that achieved and sustained high ORS coverage and those that did not. Key partners across sectors have critical roles to play to effectively address supply- and demand-side barriers. Efforts must synchronize demand generation, private provider outreach and public sector work. Many donor funds are either suspended or redirected in the event of political instability, exacerbating the health challenges faced by countries in these contexts. We found little information on the cost of scale-up efforts. We identified a number of characteristics of successful ORS scale-up programs, including involvement of a broad range of key players, addressing supply and demand generation together, and working with both public and private sectors. Dedicated efforts are needed to launch and sustain success, including monitoring and evaluation plans to track program costs and impacts. These case studies were designed to inform programmatic decision-making; thus, rigorous academic methods to qualitatively and quantitatively evaluate country ORS scale-up programs might

  12. TV Weathercasters as Climate Educators: Rationale, Evidence for Effectiveness, and Potential for Nationwide Scale-Up. (Invited)

    Science.gov (United States)

    Maibach, E.; Cullen, H. M.; Witte, J.

    2013-12-01

    local ramifications of climate change, their viewers learn. Our current attempts to scale-up the model on a limited basis - in one state as a field experiment, and elsewhere around the nation on an uncontrolled basis - are showing promise in terms of attracting an increasing numbers of participating weathercasters. Lastly, professional associations that represent TV weathercasters (AMS and NWA), and government agencies that produce climate and weather data for meteorologists (NOAA and NASA), are committed to help scale up this model so that all interested TV weathercasters have easy access to localized information through which to educate their viewers about local weather and related implications of climate change. In sum, by engaging and empowering TV weathercasters as climate educators, we seek to increase public understanding of the relationships among climate, climate variability, climate change, weather extremes and community vulnerability, and we believe this model has considerable potential.

  13. Captivity humanizes the primate microbiome.

    Science.gov (United States)

    Clayton, Jonathan B; Vangay, Pajau; Huang, Hu; Ward, Tonya; Hillmann, Benjamin M; Al-Ghalith, Gabriel A; Travis, Dominic A; Long, Ha Thang; Tuan, Bui Van; Minh, Vo Van; Cabana, Francis; Nadler, Tilo; Toddes, Barbara; Murphy, Tami; Glander, Kenneth E; Johnson, Timothy J; Knights, Dan

    2016-09-13

    The primate gastrointestinal tract is home to trillions of bacteria, whose composition is associated with numerous metabolic, autoimmune, and infectious human diseases. Although there is increasing evidence that modern and Westernized societies are associated with dramatic loss of natural human gut microbiome diversity, the causes and consequences of such loss are challenging to study. Here we use nonhuman primates (NHPs) as a model system for studying the effects of emigration and lifestyle disruption on the human gut microbiome. Using 16S rRNA gene sequencing in two model NHP species, we show that although different primate species have distinctive signature microbiota in the wild, in captivity they lose their native microbes and become colonized with Prevotella and Bacteroides, the dominant genera in the modern human gut microbiome. We confirm that captive individuals from eight other NHP species in a different zoo show the same pattern of convergence, and that semicaptive primates housed in a sanctuary represent an intermediate microbiome state between wild and captive. Using deep shotgun sequencing, chemical dietary analysis, and chloroplast relative abundance, we show that decreasing dietary fiber and plant content are associated with the captive primate microbiome. Finally, in a meta-analysis including published human data, we show that captivity has a parallel effect on the NHP gut microbiome to that of Westernization in humans. These results demonstrate that captivity and lifestyle disruption cause primates to lose native microbiota and converge along an axis toward the modern human microbiome.

  14. Captivity humanizes the primate microbiome

    Science.gov (United States)

    Vangay, Pajau; Huang, Hu; Ward, Tonya; Hillmann, Benjamin M.; Al-Ghalith, Gabriel A.; Travis, Dominic A.; Long, Ha Thang; Tuan, Bui Van; Minh, Vo Van; Cabana, Francis; Nadler, Tilo; Toddes, Barbara; Murphy, Tami; Glander, Kenneth E.; Johnson, Timothy J.; Knights, Dan

    2016-01-01

    The primate gastrointestinal tract is home to trillions of bacteria, whose composition is associated with numerous metabolic, autoimmune, and infectious human diseases. Although there is increasing evidence that modern and Westernized societies are associated with dramatic loss of natural human gut microbiome diversity, the causes and consequences of such loss are challenging to study. Here we use nonhuman primates (NHPs) as a model system for studying the effects of emigration and lifestyle disruption on the human gut microbiome. Using 16S rRNA gene sequencing in two model NHP species, we show that although different primate species have distinctive signature microbiota in the wild, in captivity they lose their native microbes and become colonized with Prevotella and Bacteroides, the dominant genera in the modern human gut microbiome. We confirm that captive individuals from eight other NHP species in a different zoo show the same pattern of convergence, and that semicaptive primates housed in a sanctuary represent an intermediate microbiome state between wild and captive. Using deep shotgun sequencing, chemical dietary analysis, and chloroplast relative abundance, we show that decreasing dietary fiber and plant content are associated with the captive primate microbiome. Finally, in a meta-analysis including published human data, we show that captivity has a parallel effect on the NHP gut microbiome to that of Westernization in humans. These results demonstrate that captivity and lifestyle disruption cause primates to lose native microbiota and converge along an axis toward the modern human microbiome. PMID:27573830

  15. On folivory, competition, and intelligence: generalisms, overgeneralizations, and models of primate evolution.

    Science.gov (United States)

    Sayers, Ken

    2013-04-01

    Considerations of primate behavioral evolution often proceed by assuming the ecological and competitive milieus of particular taxa via their relative exploitation of gross food types, such as fruits versus leaves. Although this "fruit/leaf dichotomy" has been repeatedly criticized, it continues to be implicitly invoked in discussions of primate socioecology and female social relationships and is explicitly invoked in models of brain evolution. An expanding literature suggests that such views have severely limited our knowledge of the social and ecological complexities of primate folivory. This paper examines the behavior of primate folivore-frugivores, with particular emphasis on gray langurs (traditionally, Semnopithecus entellus) within the broader context of evolutionary ecology. Although possessing morphological characteristics that have been associated with folivory and constrained activity patterns, gray langurs are known for remarkable plasticity in ecology and behavior. Their diets are generally quite broad and can be discussed in relation to Liem's Paradox, the odd coupling of anatomical feeding specializations with a generalist foraging strategy. Gray langurs, not coincidentally, inhabit arguably the widest range of habitats for a nonhuman primate, including high elevations in the Himalayas. They provide an excellent focal point for examining the assumptions and predictions of behavioral, socioecological, and cognitive evolutionary models. Contrary to the classical descriptions of the primate folivore, Himalayan and other gray langurs-and, in actuality, many leaf-eating primates-range widely, engage in resource competition (both of which have previously been noted for primate folivores), and solve ecological problems rivaling those of more frugivorous primates (which has rarely been argued for primate folivores). It is maintained that questions of primate folivore adaptation, temperate primate adaptation, and primate evolution more generally cannot be

  16. Evaluating Ecotypes as a means of Scaling-up Permafrost Thermal Measurements in Western Alaska.

    Science.gov (United States)

    Cable, William; Romanovsky, Vladimir

    2015-04-01

    In many regions, permafrost temperatures are increasing due to climate change and in some cases permafrost is thawing and degrading. In areas where degradation has already occurred the effects can be dramatic, resulting in changing ecosystems, carbon release, and damage to infrastructure. Yet in many areas we lack baseline data, such as subsurface temperatures, needed to assess future changes and potential risk areas. Besides climate, the physical properties of the vegetation cover and subsurface material have a major influence on the thermal state of permafrost. These properties are often directly related to the type of ecosystem overlaying permafrost. Thus, classifying the landscape into general ecotypes might be an effective way to scale up permafrost thermal data. To evaluate using ecotypes as a way of scaling-up permafrost thermal data within a region we selected an area in Western Alaska, the Selawik National Wildlife Refuge, which is on the boundary between continuous and discontinuous permafrost. This region was selected because previously an ecological land classification had been conducted and a very high-resolution ecotype map was generated. Using this information we selected 18 spatially distributed sites covering the most abundant ecotypes, where we are collecting low vertical resolution soil temperature data to a depth of 1.5 meters at most sites. At three additional core sites, we are collecting air temperature, snow depth, and high vertical resolution soil temperature to a depth of 3 meters. The sites were installed in the summers of 2011 and 2012; consequently, we have at least two years of data from all sites. Mean monthly and mean annual air temperature and snow depth for all three core sites are similar within the 2012-2014 period. Additionally, the average air temperature and snow depth from our three cores sites compares well with that of a nearby meteorological station for which long-term data is available. During the study period snow depth

  17. Radio-isotope production scale-up at the University of Wisconsin

    Energy Technology Data Exchange (ETDEWEB)

    Nickles, Robert Jerome [Univ of Wisconsin

    2014-06-19

    Our intent has been to scale up our production capacity for a subset of the NSAC-I list of radioisotopes in jeopardy, so as to make a significant impact on the projected national needs for Cu-64, Zr-89, Y-86, Ga-66, Br-76, I-124 and other radioisotopes that offer promise as PET synthons. The work-flow and milestones in this project have been compressed into a single year (Aug 1, 2012- July 31, 2013). The grant budget was virtually dominated by the purchase of a pair of dual-mini-cells that have made the scale-up possible, now permitting the Curie-level processing of Cu-64 and Zr-89 with greatly reduced radiation exposure. Mile stones: 1. We doubled our production of Cu-64 and Zr-89 during the grant period, both for local use and out-bound distribution to ≈ 30 labs nationwide. This involved the dove-tailing of beam schedules of both our PETtrace and legacy RDS cyclotron. 2. Implemented improved chemical separation of Zr-89, Ga-66, Y-86 and Sc-44, with remote, semi-automated dissolution, trap-and-release separation under LabView control in the two dual-mini-cells provided by this DOE grant. A key advance was to fit the chemical stream with miniature radiation detectors to confirm the transfer operations. 3. Implemented improved shipping of radioisotopes (Cu-64, Zr-89, Tc-95m, and Ho-163) with approved DOT 7A boxes, with a much-improved FedEx shipping success compared to our previous steel drums. 4. Implemented broad range quantitative trace metal analysis, employing a new microwave plasma atomic emission spectrometer (Agilent 4200) capable of ppb sensitivity across the periodic table. This new instrument will prove essential in bringing our radiometals into FDA compliance needing CoA’s for translational research in clinical trials. 5. Expanded our capabilities in target fabrication, with the purchase of a programmable 1600 oC inert gas tube furnace for the smelting of binary alloy target materials. A similar effort makes use of our RF induction furnace, allowing

  18. 'Time is costly': modelling the macroeconomic impact of scaling-up antiretroviral treatment in sub-Saharan Africa.

    Science.gov (United States)

    Ventelou, Bruno; Moatti, Jean-Paul; Videau, Yann; Kazatchkine, Michel

    2008-01-02

    Macroeconomic policy requirements may limit the capacity of national and international policy-makers to allocate sufficient resources for scaling-up access to HIV care and treatment in developing countries. An endogenous growth model, which takes into account the evolution of society's human capital, was used to assess the macroeconomic impact of policies aimed at scaling-up access to HIV/AIDS treatment in six African countries (Angola, Benin, Cameroon, Central African Republic, Ivory Coast and Zimbabwe). The model results showed that scaling-up access to treatment in the affected population would limit gross domestic product losses due to AIDS although differently from country to country. In our simulated scenarios of access to antiretroviral therapy, only 10.3% of the AIDS shock is counterbalanced in Zimbabwe, against 85.2% in Angola and even 100.0% in Benin (a total recovery). For four out of the six countries (Angola, Benin, Cameroon, Ivory Coast), the macro-economic gains of scaling-up would become potentially superior to its associated costs in 2010. Despite the variability of HIV prevalence rates between countries, macro-economic estimates strongly suggest that a massive investment in scaling-up access to HIV treatment may efficiently counteract the detrimental long-term impact of the HIV pandemic on economic growth, to the extent that the AIDS shock has not already driven the economy beyond an irreversible 'no-development epidemiological trap'.

  19. Prelude to rational scale-up of penicillin production: a scale-down study.

    Science.gov (United States)

    Wang, Guan; Chu, Ju; Noorman, Henk; Xia, Jianye; Tang, Wenjun; Zhuang, Yingping; Zhang, Siliang

    2014-03-01

    Penicillin is one of the best known pharmaceuticals and is also an important member of the β-lactam antibiotics. Over the years, ambitious yields, titers, productivities, and low costs in the production of the β-lactam antibiotics have been stepwise realized through successive rounds of strain improvement and process optimization. Penicillium chrysogenum was proven to be an ideal cell factory for the production of penicillin, and successful approaches were exploited to elevate the production titer. However, the industrial production of penicillin faces the serious challenge that environmental gradients, which are caused by insufficient mixing and mass transfer limitations, exert a considerably negative impact on the ultimate productivity and yield. Scale-down studies regarding diverse environmental gradients have been carried out on bacteria, yeasts, and filamentous fungi as well as animal cells. In accordance, a variety of scale-down devices combined with fast sampling and quenching protocols have been established to acquire the true snapshots of the perturbed cellular conditions. The perturbed metabolome information stemming from scale-down studies contributed to the comprehension of the production process and the identification of improvement approaches. However, little is known about the influence of the flow field and the mechanisms of intracellular metabolism. Consequently, it is still rather difficult to realize a fully rational scale-up. In the future, developing a computer framework to simulate the flow field of the large-scale fermenters is highly recommended. Furthermore, a metabolically structured kinetic model directly related to the production of penicillin will be further coupled to the fluid flow dynamics. A mathematical model including the information from both computational fluid dynamics and chemical reaction dynamics will then be established for the prediction of detailed information over the entire period of the fermentation process and

  20. Scaling-up of dental pulp stem cells isolated from multiple niches.

    Directory of Open Access Journals (Sweden)

    Nelson F Lizier

    Full Text Available Dental pulp (DP can be extracted from child's primary teeth (deciduous, whose loss occurs spontaneously by about 5 to 12 years. Thus, DP presents an easy accessible source of stem cells without ethical concerns. Substantial quantities of stem cells of an excellent quality and at early (2-5 passages are necessary for clinical use, which currently is a problem for use of adult stem cells. Herein, DPs were cultured generating stem cells at least during six months through multiple mechanical transfers into a new culture dish every 3-4 days. We compared stem cells isolated from the same DP before (early population, EP and six months after several mechanical transfers (late population, LP. No changes, in both EP and LP, were observed in morphology, expression of stem cells markers (nestin, vimentin, fibronectin, SH2, SH3 and Oct3/4, chondrogenic and myogenic differentiation potential, even after cryopreservation. Six hours after DP extraction and in vitro plating, rare 5-bromo-2'-deoxyuridine (BrdU positive cells were observed in pulp central part. After 72 hours, BrdU positive cells increased in number and were found in DP periphery, thus originating a multicellular population of stem cells of high purity. Multiple stem cell niches were identified in different zones of DP, because abundant expression of nestin, vimentin and Oct3/4 proteins was observed, while STRO-1 protein localization was restricted to perivascular niche. Our finding is of importance for the future of stem cell therapies, providing scaling-up of stem cells at early passages with minimum risk of losing their "stemness".

  1. Protecting HIV information in countries scaling up HIV services: a baseline study

    Directory of Open Access Journals (Sweden)

    Beck Eduard J

    2011-02-01

    Full Text Available Abstract Background Individual-level data are needed to optimize clinical care and monitor and evaluate HIV services. Confidentiality and security of such data must be safeguarded to avoid stigmatization and discrimination of people living with HIV. We set out to assess the extent that countries scaling up HIV services have developed and implemented guidelines to protect the confidentiality and security of HIV information. Methods Questionnaires were sent to UNAIDS field staff in 98 middle- and lower-income countries, some reportedly with guidelines (G-countries and others intending to develop them (NG-countries. Responses were scored, aggregated and weighted to produce standard scores for six categories: information governance, country policies, data collection, data storage, data transfer and data access. Responses were analyzed using regression analyses for associations with national HIV prevalence, gross national income per capita, OECD income, receiving US PEPFAR funding, and being a G- or NG-country. Differences between G- and NG-countries were investigated using non-parametric methods. Results Higher information governance scores were observed for G-countries compared with NG-countries; no differences were observed between country policies or data collection categories. However, for data storage, data transfer and data access, G-countries had lower scores compared with NG-countries. No significant associations were observed between country score and HIV prevalence, per capita gross national income, OECD economic category, and whether countries had received PEPFAR funding. Conclusions Few countries, including G-countries, had developed comprehensive guidelines on protecting the confidentiality and security of HIV information. Countries must develop their own guidelines, using established frameworks to guide their efforts, and may require assistance in adapting, adopting and implementing them.

  2. Protecting HIV information in countries scaling up HIV services: a baseline study.

    Science.gov (United States)

    Beck, Eduard J; Mandalia, Sundhiya; Harling, Guy; Santas, Xenophon M; Mosure, Debra; Delay, Paul R

    2011-02-06

    Individual-level data are needed to optimize clinical care and monitor and evaluate HIV services. Confidentiality and security of such data must be safeguarded to avoid stigmatization and discrimination of people living with HIV. We set out to assess the extent that countries scaling up HIV services have developed and implemented guidelines to protect the confidentiality and security of HIV information. Questionnaires were sent to UNAIDS field staff in 98 middle- and lower-income countries, some reportedly with guidelines (G-countries) and others intending to develop them (NG-countries). Responses were scored, aggregated and weighted to produce standard scores for six categories: information governance, country policies, data collection, data storage, data transfer and data access. Responses were analyzed using regression analyses for associations with national HIV prevalence, gross national income per capita, OECD income, receiving US PEPFAR funding, and being a G- or NG-country. Differences between G- and NG-countries were investigated using non-parametric methods. Higher information governance scores were observed for G-countries compared with NG-countries; no differences were observed between country policies or data collection categories. However, for data storage, data transfer and data access, G-countries had lower scores compared with NG-countries. No significant associations were observed between country score and HIV prevalence, per capita gross national income, OECD economic category, and whether countries had received PEPFAR funding. Few countries, including G-countries, had developed comprehensive guidelines on protecting the confidentiality and security of HIV information. Countries must develop their own guidelines, using established frameworks to guide their efforts, and may require assistance in adapting, adopting and implementing them.

  3. Opportunistic Computing with Lobster: Lessons Learned from Scaling up to 25k Non-Dedicated Cores

    Science.gov (United States)

    Wolf, Matthias; Woodard, Anna; Li, Wenzhao; Hurtado Anampa, Kenyi; Yannakopoulos, Anna; Tovar, Benjamin; Donnelly, Patrick; Brenner, Paul; Lannon, Kevin; Hildreth, Mike; Thain, Douglas

    2017-10-01

    We previously described Lobster, a workflow management tool for exploiting volatile opportunistic computing resources for computation in HEP. We will discuss the various challenges that have been encountered while scaling up the simultaneous CPU core utilization and the software improvements required to overcome these challenges. Categories: Workflows can now be divided into categories based on their required system resources. This allows the batch queueing system to optimize assignment of tasks to nodes with the appropriate capabilities. Within each category, limits can be specified for the number of running jobs to regulate the utilization of communication bandwidth. System resource specifications for a task category can now be modified while a project is running, avoiding the need to restart the project if resource requirements differ from the initial estimates. Lobster now implements time limits on each task category to voluntarily terminate tasks. This allows partially completed work to be recovered. Workflow dependency specification: One workflow often requires data from other workflows as input. Rather than waiting for earlier workflows to be completed before beginning later ones, Lobster now allows dependent tasks to begin as soon as sufficient input data has accumulated. Resource monitoring: Lobster utilizes a new capability in Work Queue to monitor the system resources each task requires in order to identify bottlenecks and optimally assign tasks. The capability of the Lobster opportunistic workflow management system for HEP computation has been significantly increased. We have demonstrated efficient utilization of 25 000 non-dedicated cores and achieved a data input rate of 30 Gb/s and an output rate of 500GB/h. This has required new capabilities in task categorization, workflow dependency specification, and resource monitoring.

  4. REACH: an effective catalyst for scaling up priority nutrition interventions at the country level.

    Science.gov (United States)

    Pearson, Brenda L; Ljungqvist, Björn

    2011-06-01

    Renewed Efforts Against Child Hunger (REACH) is the joint United Nations initiative to address Millennium Development Goal (MDG) 10, Target 3, i.e., to halve the proportion of underweight children under 5 years old by 2015. The United Nations Food and Agriculture Organization (FAO), the World Health Organization (WHO), the United Nations Children's Fund (UNICEF), the World Food Programme (WFP), and the International Fund for Agricultural Development (IFAD) developed and tested a facilitation mechanism to act as a catalyst for scaling up multisectoral nutrition activities. The UN-REACH partners developed pilot projects in Mauritania and Lao PDR from 2008 to 2010 and deployed facilitators to improve nutrition governance and coordination. Review missions were conducted in February 2011 to assess the REACH approach and what it achieved. The UN review mission members reviewed documents, assessed policy and management indicators, conducted qualitative interviews, and discussed findings with key stakeholders, including the most senior UN nutrition directors from all agencies. Among other UN-REACH achievements, the Prime Minister of Mauritania agreed to preside over a new National Nutrition Development Council responsible for high-level decision-making and setting national policy objectives. REACH facilitated the completion of Lao's first national Nutrition Strategy and Plan of Action and formation of the multistakeholder Nutrition Task Force. During the REACH engagement, coordination, joint advocacy, situation analysis, policy development, and joint UN programming for nutrition were strengthened in Lao PDR and Mauritania. Improvements in the nutrition governance and management mechanisms in Mauritania and Lao PDR were observed during the period of REACH support through increased awareness of nutrition as a key development objective, establishment of governmental multisectoral coordinating mechanisms, improved government capacity, and new joint UN-government nutrition

  5. Technology transfer and scale-up of the Flublok recombinant hemagglutinin (HA) influenza vaccine manufacturing process.

    Science.gov (United States)

    Buckland, Barry; Boulanger, Robert; Fino, Mireli; Srivastava, Indresh; Holtz, Kathy; Khramtsov, Nikolai; McPherson, Clifton; Meghrous, Jamal; Kubera, Paul; Cox, Manon M J

    2014-09-22

    Multiple different hemagglutinin (HA) protein antigens have been reproducibly manufactured at the 650L scale by Protein Sciences Corporation (PSC) based on an insect cell culture with baculovirus infection. Significantly, these HA protein antigens were produced by the same Universal Manufacturing process as described in the biological license application (BLA) for the first recombinant influenza vaccine approved by the FDA (Flublok). The technology is uniquely designed so that a change in vaccine composition can be readily accommodated from one HA protein antigen to another one. Here we present a vaccine candidate to combat the recently emerged H7N9 virus as an example starting with the genetic sequence for the required HA, creation of the baculovirus and ending with purified protein antigen (or vaccine component) at the 10L scale accomplished within 38 days under GMP conditions. The same process performance is being achieved at the 2L, 10L, 100L, 650L and 2500L scale. An illustration is given of how the technology was transferred from the benchmark 650L scale facility to a retrofitted microbial facility at the 2500L scale within 100 days which includes the time for facility engineering changes. The successful development, technology transfer and scale-up of the Flublok process has major implications for being ready to make vaccine rapidly on a worldwide scale as a defense against pandemic influenza. The technology described does not have the same vulnerability to mutations in the egg adapted strain, and resulting loss in vaccine efficacy, faced by egg based manufacture. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Scale-up of TB and HIV programme collaborative activities in Zambia - a 10-year review.

    Science.gov (United States)

    Kapata, N; Chanda-Kapata, P; Grobusch, M P; O'Grady, J; Schwank, S; Bates, M; Jansenn, S; Mwinga, A; Cobelens, F; Mwaba, P; Zumla, A

    2012-06-01

    To review the activities, progress, achievements and challenges of the Zambia Ministry of Health tuberculosis (TB)/HIV collaborative activities over the past decade. Analysis of Zambia Ministry of Health National TB and HIV programme documents and external independent programme review reports pertaining to 2000-2010. The number of people testing for HIV increased from 37 557 persons in 2003 to 1 327 995 persons in 2010 nationally. Those receiving anti-retroviral therapy (ART) increased from 143 in 2003 to 344 304 in 2010. The national HIV prevalence estimates declined from 14.3% in 2001 to 13.5% in 2009. The proportion of TB patients being tested for HIV increased from 22.6% in 2006 to 84% in 2010 and approximately 70% were HIV positive. The proportion of the HIV-infected TB patients who: (i) started on ART increased from 38% in 2006 to 50% in 2010; (ii) commenced co-trimoxazole preventive therapy (CPT) increased from 31% in 2006 to 70% in 2010; and (iii) were successfully treated increased to an average of 80% resulting in decline of deaths from 13% in 2006 to 9% in 2010. The scale-up of TB/HIV collaborative programme activities in Zambia has steadily increased over the past decade resulting in increased testing for TB and HIV, and anti-retroviral (ARV) rollout with improved treatment outcomes among TB patients co-infected with HIV. Getting service delivery points to adhere to WHO guidelines for collaborative TB/HIV activities remains problematic, especially those meant to reduce the burden of TB in people living with HIV/AIDS (PLWHA). © 2012 Blackwell Publishing Ltd.

  7. When does seed limitation matter for scaling up reforestation from patches to landscapes?

    Science.gov (United States)

    Caughlin, T Trevor; Elliott, Stephen; Lichstein, Jeremy W

    2016-12-01

    Restoring forest to hundreds of millions of hectares of degraded land has become a centerpiece of international plans to sequester carbon and conserve biodiversity. Forest landscape restoration will require scaling up ecological knowledge of secondary succession from small-scale field studies to predict forest recovery rates in heterogeneous landscapes. However, ecological field studies reveal widely divergent times to forest recovery, in part due to landscape features that are difficult to replicate in empirical studies. Seed rain can determine reforestation rate and depends on landscape features that are beyond the scale of most field studies. We develop mathematical models to quantify how landscape configuration affects seed rain and forest regrowth in degraded patches. The models show how landscape features can alter the successional trajectories of otherwise identical patches, thus providing insight into why some empirical studies reveal a strong effect of seed rain on secondary succession, while others do not. We show that seed rain will strongly limit reforestation rate when patches are near a threshold for arrested succession, when positive feedbacks between tree canopy cover and seed rain occur during early succession, and when directed dispersal leads to between-patch interactions. In contrast, seed rain has weak effects on reforestation rate over a wide range of conditions, including when landscape-scale seed availability is either very high or very low. Our modeling framework incorporates growth and survival parameters that are commonly estimated in field studies of reforestation. We demonstrate how mathematical models can inform forest landscape restoration by allowing land managers to predict where natural regeneration will be sufficient to restore tree cover. Translating quantitative forecasts into spatially targeted interventions for forest landscape restoration could support target goals of restoring millions of hectares of degraded land and help

  8. Interagency Collaborative Team Model for Capacity Building to Scale-Up Evidence-Based Practice.

    Science.gov (United States)

    Hurlburt, Michael; Aarons, Gregory A; Fettes, Danielle; Willging, Cathleen; Gunderson, Lara; Chaffin, Mark J

    2014-04-01

    System-wide scale up of evidence-based practice (EBP) is a complex process. Yet, few strategic approaches exist to support EBP implementation and sustainment across a service system. Building on the Exploration, Preparation, Implementation, and Sustainment (EPIS) implementation framework, we developed and are testing the Interagency Collaborative Team (ICT) process model to implement an evidence-based child neglect intervention (i.e., SafeCare®) within a large children's service system. The ICT model emphasizes the role of local agency collaborations in creating structural supports for successful implementation. We describe the ICT model and present preliminary qualitative results from use of the implementation model in one large scale EBP implementation. Qualitative interviews were conducted to assess challenges in building system, organization, and home visitor collaboration and capacity to implement the EBP. Data collection and analysis centered on EBP implementation issues, as well as the experiences of home visitors under the ICT model. Six notable issues relating to implementation process emerged from participant interviews, including: (a) initial commitment and collaboration among stakeholders, (b) leadership, (c) communication, (d) practice fit with local context, (e) ongoing negotiation and problem solving, and (f) early successes. These issues highlight strengths and areas for development in the ICT model. Use of the ICT model led to sustained and widespread use of SafeCare in one large county. Although some aspects of the implementation model may benefit from enhancement, qualitative findings suggest that the ICT process generates strong structural supports for implementation and creates conditions in which tensions between EBP structure and local contextual variations can be resolved in ways that support the expansion and maintenance of an EBP while preserving potential for public health benefit.

  9. SCALING UP A MOBILE TELEMEDICINE SOLUTION IN BOTSWANA: KEYS TO SUSTAINABILITY

    Directory of Open Access Journals (Sweden)

    Kagiso eNdlovu

    2014-12-01

    Full Text Available Effective health care delivery is significantly compromised in an environment where resources, both human and technical, are limited. Botswana’s health care system is one of the many in the African continent with few specialised medical doctors, thereby posing a barrier to patients’ access to health care services. In addition, the traditional landline and non-robust Information Technology (IT network infrastructure characterised by slow bandwidth still dominates the health care system in Botswana. Upgrading of the landline IT infrastructure to meet today’s health care demands is a tedious, long and expensive process. Despite these challenges, there still lies hope in health care delivery utilising wireless telecommunication services. Botswana has recently experienced a tremendous growth in the mobile telecommunication industry coupled with an increase in the number of individually owned mobile devices. This growth inspired the Botswana-UPenn Partnership (BUP to collaborate with local partners to explore using mobile devices as tools to improve access to specialised health care delivery. Pilot studies were conducted across four medical specialties, including radiology, oral medicine, dermatology and cervical cancer screening. Findings from the studies became vital evidence in support of the first scale-up project of a mobile telemedicine solution in Botswana, also known as Kgonafalo. Some technical and social challenges were encountered during the initial studies, such as malfunctioning of mobile devices, accidental damage of devices and cultural misalignment between IT and healthcare providers. These challenges brought about lessons learnt, including a strong need for unwavering senior management support, establishment of solid local public-private partnerships, and efficient project sustainability plans. Sustainability milestones included the development and signing of a Memorandum of Understanding (MOU between the Botswana government and

  10. Scale-Up Design Analysis and Modelling of Cobalt Oxide Silica Membrane Module for Hydrogen Processing

    Directory of Open Access Journals (Sweden)

    Guozhao Ji

    2013-08-01

    Full Text Available This work shows the application of a validated mathematical model for gas permeation at high temperatures focusing on demonstrated scale-up design for H2 processing. The model considered the driving force variation with spatial coordinates and the mass transfer across the molecular sieve cobalt oxide silica membrane to predict the separation performance. The model was used to study the process of H2 separation at 500 °C in single and multi-tube membrane modules. Parameters of interest included the H2 purity in the permeate stream, H2 recovery and H2 yield as a function of the membrane length, number of tubes in a membrane module, space velocity and H2 feed molar fraction. For a single tubular membrane, increasing the length of a membrane tube led to higher H2 yield and H2 recovery, owing to the increase of the membrane area. However, the H2 purity decreased as H2 fraction was depleted, thus reducing the driving force for H2 permeation. By keeping the membrane length constant in a multi-tube arrangement, the H2 yield and H2 recovery increase was attributed to the higher membrane area, but the H2 purity was again compromised. Increasing the space velocity avoided the reduction of H2 purity and still delivered higher H2 yield and H2 recovery than in a single membrane arrangement. Essentially, if the membrane surface is too large, the driving force becomes lower at the expense of H2 purity. In this case, the membrane module is over designed. Hence, maintaining a driving force is of utmost importance to deliver the functionality of process separation.

  11. Scaling-up the biomass production of Cymbopogon citratus L. in temporary immersion system

    Directory of Open Access Journals (Sweden)

    Elisa Quiala

    2014-04-01

    Full Text Available Shoot-tips, collected from greenhouse-grown plants of Cymbopogon citratus L. (lemmon grass, were incubated on a semi-solid Murashige and Skoog (MS medium with 30% (w/v sucrose, and supplemented with 0.89 µM 6-benzyladenine (BA. After three weeks of culture shoots were individualized and then inoculated in 10 litres temporary immersion system (TIS containing 3 litres of the same basal MS liquid medium. The effects of three immersion frequency (immersion every 12, 6 and 4 hours on the production of biomass were studied. Three inoculum densities (forty, fifty and sixty shoots/TIS were also tested. The biomass growth was inûuenced by the immersion frequency. The highest proliferation rate (17.3 shoots/explants and the plant length (45.2 cm were obtained in plants immersed every 4 h. Also, the fresh and dry biomass weight (153.4 gFW and 24.8 gDW, respectively were higher in this treatment. The maximum biomass accumulation (185.2 gFW and 35.2 gDW was achieved after 30 days of culture when an inoculum density of 60 explants per TIS was used. For the first time, biomass of C. citratus has been produced in10 litres TIS. These results represent the first step in the scaling-up the biomass production of this medicinal plant in large temporary immersion bioreactors. Key words: automation, biomass growth, lemmon grass medicinal plant, tissue culture

  12. Constraints to exclusive breastfeeding practice among breastfeeding mothers in Southwest Nigeria: implications for scaling up

    Directory of Open Access Journals (Sweden)

    Agunbiade Ojo M

    2012-04-01

    , scaling up of exclusive breastfeeding among mothers requires concerted efforts at the macro, meso and micro levels of the Nigerian society.

  13. The Design and Scale-Up of Multiple-Impeller Fermenters for Liquid Film Controlled Processes

    Directory of Open Access Journals (Sweden)

    Labík, L.

    2013-05-01

    Full Text Available Mechanically agitated gas-liquid contactors are frequently used in the chemical, food and biochemical industries as fermenters and as hydrogenation or chlorination reactors. However wide is the usage of such vessels, their design is not based on chemical engineering data, but is still rather empirical. Thus, it is highly desirable to have a tool for the rational design of agitated gas-liquid contactors that is based on fundamental chemical engineering parameters that are transferable to other systems and operating conditions. Focusing on liquid film-controlled processes and using the data from fermenters of different scales, we develop kLa correlations that are suitable for scale-up. First, we discuss how to determine the proper experimental kLa values, which are not distorted by other equipment parameters as is the gas residence time. We demonstrate the possible kLa distortion on the pilot-plant experimental data by comparing the results obtained by two different experimental techniques. Further, we present physically correct kLa data for fully non-coalescent (sodium sulphate solution batch. The data are presented both for laboratory and pilot-plant fermenters. We identify the process parameters, the values of which are dependent on the vessel scale when operated under the same power input per volume, and, using these parameters, we develop common kLa correlations suitable to describe the data for various scales of the vessel. The correlations developed reduce the uncertainty in predicting the volume of industrial scale fermenters from almost 1/2 to 1/4 of their total volume, thereby enabling significant reductions in both the initial costs, and operating costs.

  14. Ultrasound assisted acid catalyzed lactose hydrolysis: Understanding into effect of operating parameters and scale up studies.

    Science.gov (United States)

    Gajendragadkar, Chinmay N; Gogate, Parag R

    2017-07-01

    The current work deals with the value addition of lactose by transforming into hydrolyzed lactose syrup containing glucose and galactose in major proportion using the novel approach of ultrasound assisted acid catalyzed lactose hydrolysis. The hydrolysis of lactose was performed in ultrasonic bath (33kHz) at 50% duty cycle at different temperatures as 65°C and 70°C and two different hydrochloric acid (HCl) concentrations as 2.5N and 3N. It was observed that acid concentration, temperature and ultrasonic treatment were the major factors in deciding the time required to achieve ∼90% hydrolysis. The ultrasonic assisted approach resulted in reduction in the reaction time and the extent of intensification was established to be dependent on the temperature, acid concentration and time of ultrasonic exposure. It was observed that the maximum process intensification obtained by introduction of ultrasound in the lactose hydrolysis process performed at 70°C and 3N HCl was reduction in the required time for ∼90% hydrolysis from 4h (without the presence of ultrasound) to 3h. The scale-up study was also performed using an ultrasonic bath with longitudinal horn (36kHz as operating frequency) at 50% duty cycle, optimized temperature of 70°C and acid concentration of 3N. It was observed that the reaction was faster in the presence of ultrasound and stirring by axial impeller at rpm of 225±25. The time required to complete ∼90% of hydrolysis remained almost the same as observed for small scale study on ultrasonic bath (33kHz) at 50% duty cycle. The use of recovered lactose from whey samples instead of pure lactose did not result in any significant changes in the progress of hydrolysis, confirming the efficacy of the selected approach. Overall, the work has presented a novel ultrasound assisted approach for intensified lactose hydrolysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Interagency Collaborative Team Model for Capacity Building to Scale-Up Evidence-Based Practice

    Science.gov (United States)

    Hurlburt, Michael; Aarons, Gregory A; Fettes, Danielle; Willging, Cathleen; Gunderson, Lara; Chaffin, Mark J

    2015-01-01

    Background System-wide scale up of evidence-based practice (EBP) is a complex process. Yet, few strategic approaches exist to support EBP implementation and sustainment across a service system. Building on the Exploration, Preparation, Implementation, and Sustainment (EPIS) implementation framework, we developed and are testing the Interagency Collaborative Team (ICT) process model to implement an evidence-based child neglect intervention (i.e., SafeCare®) within a large children’s service system. The ICT model emphasizes the role of local agency collaborations in creating structural supports for successful implementation. Methods We describe the ICT model and present preliminary qualitative results from use of the implementation model in one large scale EBP implementation. Qualitative interviews were conducted to assess challenges in building system, organization, and home visitor collaboration and capacity to implement the EBP. Data collection and analysis centered on EBP implementation issues, as well as the experiences of home visitors under the ICT model. Results Six notable issues relating to implementation process emerged from participant interviews, including: (a) initial commitment and collaboration among stakeholders, (b) leadership, (c) communication, (d) practice fit with local context, (e) ongoing negotiation and problem solving, and (f) early successes. These issues highlight strengths and areas for development in the ICT model. Conclusions Use of the ICT model led to sustained and widespread use of SafeCare in one large county. Although some aspects of the implementation model may benefit from enhancement, qualitative findings suggest that the ICT process generates strong structural supports for implementation and creates conditions in which tensions between EBP structure and local contextual variations can be resolved in ways that support the expansion and maintenance of an EBP while preserving potential for public health benefit. PMID:27512239

  16. Scaling-up of Energy Services Access in East Africa to achieve the Millennium Development Goals

    Energy Technology Data Exchange (ETDEWEB)

    Arvidson, Anders; Nordstroem, Mattias; Forslund, Helena; Syngellakis, Katerina; Marcel, Jean-Christian; Woodsworth, Gregory; Songela, Francis; Sawe, Estomih; Ngigi, Ashington; Macharia, Daniel; Ngoye, Elizabeth

    2006-06-15

    From the 13th to the 15th March 2006, the ENABLE team together with UNDP facilitated a three day consultative workshop hosted by the East African Community. The principal objective of this workshop was to facilitate the design of a regional energy access workplan and accompanying investment programmes to support the achievement of the millennium development goals. The workshop brought together almost 50 stakeholders from the East African region, representing various sectors (health, education, water, agriculture, environment, finance, etc.), organisations (public, private and NGOs) and donors, with the objective to identify and recommend actions that need to be undertaken in East Africa at regional, national and local levels in order to achieve the EAC Regional Energy Access Scale-up targets endorsed by the Ministers of Energy of Kenya, Tanzania and Uganda in August 2005. In order to generate new and substantive information during the three days, a highly interactive and participatory approach was used, where participants worked intensively in small groups with a set of questions which examined the issues and actions needed to achieve the four EAC Regional Energy Access Scale-up targets, as listed below: Target 1: Enable the use of modern fuels for 50% of those who at present use traditional biomass for cooking. Support efforts to develop and adopt the use of improved cook stoves, means to reduce indoor air pollution, and measures to increase sustainable biomass production. Target 2: Access to reliable modern energy services for all urban and peri-urban poor. Target 3: Electricity for services such as lighting, refrigeration, information and communication technology, and water treatment and supply for schools, clinics, hospitals and community centres. Target 4: Access to mechanical power within the community for all communities for productive uses. The main output from the workshop was a set of interventions for each of the energy access scale-up targets

  17. CFD analysis of the flow-field scale-up influence on the electrodes performance in a PEFC

    Energy Technology Data Exchange (ETDEWEB)

    Squadrito, G.; Barbera, O.; Gatto, I.; Giacoppo, G.; Urbani, F.; Passalacqua, E. [CNR-ITAE, via Salita S. Lucia sopra Contessen. 5, 98126 S. Lucia, Messina (Italy)

    2005-12-01

    A computational fluid dynamic (CFD) analysis was used as a useful tool to obtain numerical relationships among similar flow-field designs having different active areas. Assuming that, at fixed current density, the porous layer velocity distribution calculated for the smallest size geometry was the optimal, a scale-up methodology has been proposed and implemented in software. It allows acquisition of the scaled-up flow-field by multiplying the reference cell parameters by suitable factors (scale factors). A calibration methodology has also been proposed by the introduction of a feedback factor evaluated by CFD analysis. A first application of this procedure has been carried out to scale-up a 5-125cm{sup 2} cell. (author)

  18. The impact and cost of scaling up midwifery and obstetrics in 58 low- and middle-income countries.

    Directory of Open Access Journals (Sweden)

    Linda Bartlett

    Full Text Available BACKGROUND AND METHODS: To guide achievement of the Millennium Development Goals, we used the Lives Saved Tool to provide a novel simulation of potential maternal, fetal, and newborn lives and costs saved by scaling up midwifery and obstetrics services, including family planning, in 58 low- and middle-income countries. Typical midwifery and obstetrics interventions were scaled to either 60% of the national population (modest coverage or 99% (universal coverage. FINDINGS: Under even a modest scale-up, midwifery services including family planning reduce maternal, fetal, and neonatal deaths by 34%. Increasing midwifery alone or integrated with obstetrics is more cost-effective than scaling up obstetrics alone; when family planning was included, the midwifery model was almost twice as cost-effective as the obstetrics model, at $2,200 versus $4,200 per death averted. The most effective strategy was the most comprehensive: increasing midwives, obstetricians, and family planning could prevent 69% of total deaths under universal scale-up, yielding a cost per death prevented of just $2,100. Within this analysis, the interventions which midwifery and obstetrics are poised to deliver most effectively are different, with midwifery benefits delivered across the continuum of pre-pregnancy, prenatal, labor and delivery, and postpartum-postnatal care, and obstetrics benefits focused mostly on delivery. Including family planning within each scope of practice reduced the number of likely births, and thus deaths, and increased the cost-effectiveness of the entire package (e.g., a 52% reduction in deaths with midwifery and obstetrics increased to 69% when family planning was added; cost decreased from $4,000 to $2,100 per death averted. CONCLUSIONS: This analysis suggests that scaling up midwifery and obstetrics could bring many countries closer to achieving mortality reductions. Midwives alone can achieve remarkable mortality reductions, particularly when they

  19. Chapter 6. Scaling Up Solutions to State, National and Global Levels

    Directory of Open Access Journals (Sweden)

    Daniel Kammen

    2016-12-01

    Full Text Available Scaling-up solutions require learning and adapting lessons between locations and at different scales. To accomplish this, common metrics are vital to building a shared language. For California, this has meant careful financial, cradle-to-grave life-cycle assessment methods leading to carbon accounting in many avenues of government (via the Low Carbon Fuel Standard or the Cap and Trade program. These methods themselves interact, such as the use of carbon accounting for the resources needed to manage water and other key resources; the use of criteria air pollution monitoring to identify environmental injustices; and the use of carbon market revenues to address these inequalities, through investment in best available abatement technologies (BACT and in job creation in disadvantaged communities anticipated in the emerging clean energy sector.  Creating interdisciplinary partnerships across the UC Campuses and the National Laboratories to innovate science and technology is critical to scalable carbon neutrality solutions. As an example, we can build coordinated research and development programs across UC and California, with strong partnerships with the Federal government to coordinate and “multiply” resources that accelerate development and deployment. These partnerships should be strongly goal-focused, i.e., they are created to solve specific, large problems, to enable quantitatively measurable outcomes within energy generation, efficiency and CO2 abatement categories. Intersectoral partnerships should be fostered across campuses, laboratories, with state, federal and multi-lateral organizations funding to develop technologies and deploy solutions at scale. Integrated partnerships with industry are required to influence markets, deploy solutions, and create new industries and jobs.  Beyond California, we need to establish consortia with industry and foundations to deploy solutions at the regional, state, national, and international scale to

  20. The success factors of scaling-up Estonian sexual and reproductive health youth clinic network--from a grassroots initiative to a national programme 1991-2013

    NARCIS (Netherlands)

    Kempers, J.P.; Ketting, E.; Chandra-Mouli, V.; Raudsepp, T.

    2015-01-01

    BACKGROUND: A growing number of middle-income countries are scaling up youth-friendly sexual and reproductive health pilot projects to national level programmes. Yet, there are few case studies on successful national level scale-up of such programmes. Estonia is an excellent example of scale-up of a

  1. On folivory, competition, and intelligence: generalism, overgeneralizations, and models of primate evolution

    Science.gov (United States)

    Sayers, Ken

    2013-01-01

    Considerations of primate behavioral evolution often proceed by assuming the ecological and competitive milieus of particular taxa via their relative exploitation of gross food types, such as fruits versus leaves. Although this “fruit/leaf dichotomy” has been repeatedly criticized, it continues to be implicitly invoked in discussions of primate socioecology and female social relationships, and explicitly invoked in models of brain evolution. An expanding literature suggests that such views have severely limited our knowledge of the social and ecological complexities of primate folivory. This paper examines the behavior of primate folivore-frugivores, with particular emphasis on gray langurs (traditionally, Semnopithecus entellus) within the broader context of evolutionary ecology. Although possessing morphological characters that have been associated with folivory and constrained activity patterns, gray langurs are known for remarkable plasticity in ecology and behavior. Their diets are generally quite broad and can be discussed in relation to “Liem’s paradox,” the odd coupling of anatomical feeding specializations with a generalist foraging strategy. Gray langurs, not coincidentally, inhabit arguably the widest range of habitats for a nonhuman primate, including high elevations in the Himalayas. They provide an excellent focal point for examining the assumptions and predictions of behavioral, socioecological, and cognitive evolutionary models. Contrary to the classical descriptions of the primate folivore, Himalayan and other gray langurs—and, in actuality, many leaf eating primates—range widely and engage in resource competition (both of which have previously been noted for primate folivores) as well as solve ecological problems rivaling those of more frugivorous primates (which has rarely been argued for primate folivores). It is maintained that questions of primate folivore adaptation, temperate primate adaptation, and primate evolution more

  2. A molecular phylogeny of living primates.

    Directory of Open Access Journals (Sweden)

    Polina Perelman

    2011-03-01

    Full Text Available Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (~8 Mb from 186 primates representing 61 (~90% of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species.

  3. A Molecular Phylogeny of Living Primates

    Science.gov (United States)

    Perelman, Polina; Johnson, Warren E.; Roos, Christian; Seuánez, Hector N.; Horvath, Julie E.; Moreira, Miguel A. M.; Kessing, Bailey; Pontius, Joan; Roelke, Melody; Rumpler, Yves; Schneider, Maria Paula C.; Silva, Artur; O'Brien, Stephen J.; Pecon-Slattery, Jill

    2011-01-01

    Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (∼8 Mb) from 186 primates representing 61 (∼90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species. PMID:21436896

  4. School Processes That Can Drive Scaling-Up of an Innovation, or Contribute to Its Abandonment. Conference Paper

    Science.gov (United States)

    Zacamy, Jenna; Newman, Denis; Lazarev, Valeriy; Lin, Li

    2015-01-01

    This paper reports findings from a multi-year study of the scale-up of Reading Apprenticeship (RA), an approach to improve academic literacy by helping teachers provide the support students need to be successful readers in the content areas. WestEd's Strategic Literacy Initiative (SLI), began developing the program in 1995 and has since reached…

  5. Collaboration, negotiation, and coalescence for interagency-collaborative teams to scale-up evidence-based practice.

    Science.gov (United States)

    Aarons, Gregory A; Fettes, Danielle L; Hurlburt, Michael S; Palinkas, Lawrence A; Gunderson, Lara; Willging, Cathleen E; Chaffin, Mark J

    2014-01-01

    Implementation and scale-up of evidence-based practices (EBPs) is often portrayed as involving multiple stakeholders collaborating harmoniously in the service of a shared vision. In practice, however, collaboration is a more complex process that may involve shared and competing interests and agendas, and negotiation. The present study examined the scale-up of an EBP across an entire service system using the Interagency Collaborative Team approach. Participants were key stakeholders in a large-scale county-wide implementation of an EBP to reduce child neglect, SafeCare. Semistructured interviews and/or focus groups were conducted with 54 individuals representing diverse constituents in the service system, followed by an iterative approach to coding and analysis of transcripts. The study was conceptualized using the Exploration, Preparation, Implementation, and Sustainment framework. Although community stakeholders eventually coalesced around implementation of SafeCare, several challenges affected the implementation process. These challenges included differing organizational cultures, strategies, and approaches to collaboration; competing priorities across levels of leadership; power struggles; and role ambiguity. Each of the factors identified influenced how stakeholders approached the EBP implementation process. System-wide scale-up of EBPs involves multiple stakeholders operating in a nexus of differing agendas, priorities, leadership styles, and negotiation strategies. The term collaboration may oversimplify the multifaceted nature of the scale-up process. Implementation efforts should openly acknowledge and consider this nexus when individual stakeholders and organizations enter into EBP implementation through collaborative processes.

  6. A Scale-up Approach for Film Coating Process Based on Surface Roughness as the Critical Quality Attribute.

    Science.gov (United States)

    Yoshino, Hiroyuki; Hara, Yuko; Dohi, Masafumi; Yamashita, Kazunari; Hakomori, Tadashi; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

    2018-01-05

    Scale-up approaches for film coating process have been established for each type of film coating equipment from thermodynamic and mechanical analyses for several decades. The objective of the present study was to establish a versatile scale-up approach for film coating process applicable to commercial production that is based on critical quality attribute (CQA) using the Quality by Design (QbD) approach and is independent of the equipment used. Experiments on a pilot scale using the Design of Experiment (DoE) approach were performed to find a suitable CQA from surface roughness, contact angle, color difference, and coating film properties by terahertz spectroscopy. Surface roughness was determined to be a suitable CQA from a quantitative appearance evaluation. When surface roughness was fixed as the CQA, the water content of the film-coated tablets was determined to be the critical material attribute (CMA), a parameter that does not depend on scale or equipment. Finally, to verify the scale-up approach determined from the pilot scale, experiments on a commercial scale were performed. The good correlation between the surface roughness (CQA) and the water content (CMA) identified at the pilot scale was also retained at the commercial scale, indicating that our proposed method should be useful as a scale-up approach for film coating process.

  7. Scale-up of a suspension-like polymerization process for the microencapsulation of phase change materials.

    Science.gov (United States)

    Sánchez-Silva, Luz; Carmona, Manuel; de Lucas, Antonio; Sánchez, Paula; Rodríguez, Juan F

    2010-01-01

    Microcapsules of polystyrene with a high level of encapsulated paraffin wax and a narrow size distribution were prepared by a suspension-like polymerization process. The scale-up of this microencapsulation process was carried out by designing a pilot plant that was geometrically proportional to that used on the laboratory scale with the aim of preparing microcapsules with a similar particle size and with the same phase change material (PCM) content as those obtained in the laboratory. In order to verify the effectiveness of the scale-up procedure, a number of experiments on the pilot plant were carried out using the optimal formulation found on the laboratory scale. Only slight differences in mean particle size and encapsulated paraffin content were observed between the two scales at higher stirring rates. The experimental values were fitted to the theoretical expression for the average dissipation rate as a function of the mean particle size. This showed that the classical nonintermittent Kolmogoroff theory is applicable on the laboratory scale, whereas in the pilot plant a large intermittence took place, thus limiting the scale-up to higher stirring rates at which an equal average dissipation rate in both scales led to the same mean particle size. The final results indicated that the assumptions made during the scale-up process were correct.

  8. Scaling up Corporate Social Investments in Education: Five Strategies That Work. Global Views. Policy Paper 2012-01

    Science.gov (United States)

    van Fleet, Justin W.

    2012-01-01

    Scaling up good corporate social investment practices in developing countries is crucial to realizing the "Education for All" and "Millennium Development Goals". Yet very few corporate social investments have the right mix of vision, financing, cross-sector engagement and leadership to come to scale. Globally, 67 million…

  9. Validation of a model for process development and scale-up of packed-bed solid-state bioreactors

    NARCIS (Netherlands)

    Weber, F.J.; Oostra, J.; Tramper, J.; Rinzema, A.

    2002-01-01

    We have validated our previously described model for scale-up of packed-bed solid-state fermenters (Weber et al., 1999) with experiments in an adiabatic 15-dm3 packed-bed reactor, using the fungi Coniothyrium minitans and Aspergillus oryzae. Effects of temperature on respiration, growth, and

  10. A novel Online-to-Offline (O2O model for pre-exposure prophylaxis and HIV testing scale up

    Directory of Open Access Journals (Sweden)

    Tarandeep Anand

    2017-01-01

    Conclusions: Adam’s Love O2O model is highly effective in linking online at-risk MSM and TG to PrEP and HIV testing services, and has high potential to be replicated and scaled up in other settings with high Internet penetration among key populations.

  11. Fenton chemistry-based detemplation of an industrially relevant microcrystalline beta zeolite. Optimization and scaling-up studies

    NARCIS (Netherlands)

    Ortiz-Iniesta, Maria Jesus; Melian-Cabrera, Ignacio

    A mild template removal of microcrystalline beta zeolite, based on Fenton chemistry, was optimized. Fenton detemplation was studied in terms of applicability conditions window, reaction rate and scale up. TGA and CHN elemental analysis were used to evaluate the detemplation effectiveness, while 'CP,

  12. High Temperature Syngas Cleanup Technology Scale-up and Demonstration Project

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, Ben [Research Triangle Inst. (RTI), Research Triangle Park, NC (United States); Turk, Brian [Research Triangle Inst. (RTI), Research Triangle Park, NC (United States); Denton, David [Research Triangle Inst. (RTI), Research Triangle Park, NC (United States); Gupta, Raghubir [Research Triangle Inst. (RTI), Research Triangle Park, NC (United States)

    2015-09-30

    Gasification is a technology for clean energy conversion of diverse feedstocks into a wide variety of useful products such as chemicals, fertilizers, fuels, electric power, and hydrogen. Existing technologies can be employed to clean the syngas from gasification processes to meet the demands of such applications, but they are expensive to build and operate and consume a significant fraction of overall parasitic energy requirements, thus lowering overall process efficiency. RTI International has developed a warm syngas desulfurization process (WDP) utilizing a transport-bed reactor design and a proprietary attrition-resistant, high-capacity solid sorbent with excellent performance replicated at lab, bench, and pilot scales. Results indicated that WDP technology can improve both efficiency and cost of gasification plants. The WDP technology achieved ~99.9% removal of total sulfur (as either H2S or COS) from coal-derived syngas at temperatures as high as 600°C and over a wide range of pressures (20-80 bar, pressure independent performance) and sulfur concentrations. Based on the success of these tests, RTI negotiated a cooperative agreement with the U.S. Department of Energy for precommercial testing of this technology at Tampa Electric Company’s Polk Power Station IGCC facility in Tampa, Florida. The project scope also included a sweet water-gas-shift process for hydrogen enrichment and an activated amine process for 90+% total carbon capture. Because the activated amine process provides some additional non-selective sulfur removal, the integration of these processes was expected to reduce overall sulfur in the syngas to sub-ppmv concentrations, suitable for most syngas applications. The overall objective of this project was to mitigate the technical risks associated with the scale up and integration of the WDP and carbon dioxide capture technologies, enabling subsequent commercial-scale demonstration. The warm syngas cleanup pre-commercial test unit

  13. Scale-up of two-phase flow in heterogeneous chalk. Matrix properties

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-02-01

    This investigation presents scale-up of a detailed heterogeneous geostatistical model to a full field reservoir simulation model, considering both single and two-phase flow properties. The model represents a typical low permeability Danish North Sea chalk reservoir and includes capillary pressure and saturation end-point variations. Two new up-scaling methods has been investigated, all based on fine scale simulation on a cross section of the geomodel. The first methods assumes piston style behaviour and a coupled viscosity is introduced into the basic Darcy`s equations. The second method is a modification of the JBN method traditionally applied in analysing results from core flooding experiments, which emerged as the most successful and therefore also the recommended method. 1. In addition to the up scaling work we review the Equivalent Radius Method for capillary pressure normalisation with explicit derivation of type functions for Maastrichtian and Danian chalk types. Implementation of the Equivalent Radiuo Method in the COSI reservoir simulator by an optikal set of key-words. There are six specific results from this work: 1. The equivalent radius method is robust to changes of scale and yields model initialisations by initial and irreducible water saturations on a full field simulation scale that agree well with values derived from averaging on a fine-scale. 2. The residual oil saturations are strongly scale dependent and the description of the residual oil as a function of the irreducible water is not applicable on a full field scale and will lead to an overestimation of the residual oil present in the reservoir. The effective residual oil saturations on a full field-scale must be considered functions of the effective initial water saturations, in order to take into account fine-scale variations in the oil/water contacts. 3. The effective permeability as calculated by statistical averages does not differ seriously from results obtained by fine-grid numerical

  14. Solar thermal production of zinc - Final steps toward scale-up - Final report

    Energy Technology Data Exchange (ETDEWEB)

    Meier, A.

    2008-05-15

    A 10 kW receiver-reactor prototype (called ZIRRUS) was further improved and tested for the solar thermal de-composition of ZnO, which is the 1{sup st} step of the two-step water-splitting thermochemical ZnO/Zn cycle. The rotating cylindrical cavity was made of either sintered ZnO or sintered Al{sub 2}O{sub 3} tiles placed on top of a multi-layer Al{sub 2}O{sub 3}-SiO{sub 2}-Y{sub 2}O{sub 3}-based ceramics for thermal shock resistance, mechanical stability, gas diffusion barrier, and thermal insulation. Pre-heated Ar gas was injected for aerodynamic window protection and for minimizing recombination of product gases in the cavity. Experimentation was carried out at PSI's High-Flux Solar Simulator with the direct heating 10 kW reactor prototype subjected to peak radiative fluxes exceeding 5,800 suns. The reactor operated without incident for a total of more than 40 h at maximum temperatures - measured behind the ZnO and Al{sub 2}O{sub 3} tiles - ranging from 1807-1907 K. Thermal dissociation of ZnO(s) near 2000 K was demonstrated for experimental runs over 4 h in transient ablation mode with up to nine semi-continuous feed cycles of ZnO particles. A working Zn/O{sub 2} separation device based on the rapid quenching of the Zn/O{sub 2} mixture is ready to be incorporated at the exit of the solar reactor. Zinc yields of up to 94% were obtained when using total Ar/Zn(g) dilution of 530 and a cooling rate of about 10{sup 5} K/s. The fully integrated solar reactor will be scaled up to the pilot scale of 100 kW. A newly developed reactor model that couples radiation, conduction, and convection heat transfer to the reaction kinetics will allow determining optimal operational conditions for matching the feeding rate to the reaction rate and for maximizing solar-to-chemical energy conversion efficiency. The 2{sup nd} step of the ZnO/Zn cycle has been experimentally demonstrated at ETH using an aerosol-flow reactor for in-situ formation and hydrolysis of Zn nanoparticles

  15. Color vision in primates: Neurobiology and behavior

    OpenAIRE

    Skalníková, Petra

    2015-01-01

    Trichromacy is the condition that involves three independent channels for processing color information based on three different cone types. Most mammals have dichromatic vision, trichromacy appears in primates of the Old World (including human) and partly in the New Wold primates. This thesis focuses on the mechanisms of trichromatic vision, its evolution in primates and the comparison of the primates of the Old and New World. The neuronal mechanisms underlying both trichromatic and dichromat...

  16. Catalyzing the scale-up of community-based primary healthcare in a rural impoverished region of northern Ghana.

    Science.gov (United States)

    Awoonor-Williams, John Koku; Phillips, James F; Bawah, Ayaga A

    2016-10-01

    Ghana's Community-based Health Planning and Services (CHPS) initiative develops accessible healthcare with participatory community support, using strategies developed and tested by a project of the Navrongo Health Research Centre. In 1996, the project was expanded to a district-wide four-celled trial. In response to evidence that strategies could reduce fertility and childhood mortality, a replication project was launched to develop methods for scale-up. Based on experience gained, CHPS scale-up was launched in 2000. Although CHPS now reaches all of Ghana's districts, the pace of scale-up within districts has been slow. In response, the Ministry of Health conducted a review of factors that constrain CHPS scale-up and problems that detract from its original evidence-based design. To resolve problems that were identified, a project was launched in 2010 to test means of accelerating CHPS scale-up and expand its range of care. Known as the Ghana Essential Health Interventions Program (GEHIP), the project provided catalytic revenue to four treatment district managers for 3 years, in conjunction with implementation of strategies for comprehensive leadership development and community partnership. Monitoring systems were developed to gauge CHPS coverage time trends in all nine study districts. GEHIP successfully accelerated CHPS implementation, producing 100% of its targeted community coverage within 5 years of implementation. Coverage in comparison districts also improved. However, the rate of coverage and per cent of the population reached by CHPS in comparison districts was only half that of GEHIP districts. GEHIP success in completing CHPS coverage represents the initial stage of a national program for strengthening community health systems in Ghana. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Impact monitoring of the national scale up of zinc treatment for childhood diarrhea in Bangladesh: repeat ecologic surveys.

    Directory of Open Access Journals (Sweden)

    Charles P Larson

    2009-11-01

    Full Text Available BACKGROUND: Zinc treatment of childhood diarrhea has the potential to save 400,000 under-five lives per year in lesser developed countries. In 2004 the World Health Organization (WHO/UNICEF revised their clinical management of childhood diarrhea guidelines to include zinc. The aim of this study was to monitor the impact of the first national campaign to scale up zinc treatment of childhood diarrhea in Bangladesh. METHODS/FINDINGS: Between September 2006 to October 2008 seven repeated ecologic surveys were carried out in four representative population strata: mega-city urban slum and urban nonslum, municipal, and rural. Households of approximately 3,200 children with an active or recent case of diarrhea were enrolled in each survey round. Caretaker awareness of zinc as a treatment for childhood diarrhea by 10 mo following the mass media launch was attained in 90%, 74%, 66%, and 50% of urban nonslum, municipal, urban slum, and rural populations, respectively. By 23 mo into the campaign, approximately 25% of urban nonslum, 20% of municipal and urban slum, and 10% of rural under-five children were receiving zinc for the treatment of diarrhea. The scale-up campaign had no adverse effect on the use of oral rehydration salt (ORS. CONCLUSIONS: Long-term monitoring of scale-up programs identifies important gaps in coverage and provides the information necessary to document that intended outcomes are being attained and unintended consequences avoided. The scale-up of zinc treatment of childhood diarrhea rapidly attained widespread awareness, but actual use has lagged behind. Disparities in zinc coverage favoring higher income, urban households were identified, but these were gradually diminished over the two years of follow-up monitoring. The scale up campaign has not had any adverse effect on the use of ORS. Please see later in the article for the Editors' Summary.

  18. Scaling up paediatric HIV care with an integrated, family-centred approach: an observational case study from Uganda.

    Science.gov (United States)

    Luyirika, Emmanuel; Towle, Megan S; Achan, Joyce; Muhangi, Justus; Senyimba, Catherine; Lule, Frank; Muhe, Lulu

    2013-01-01

    Family-centred HIV care models have emerged as an approach to better target children and their caregivers for HIV testing and care, and further provide integrated health services for the family unit's range of care needs. While there is significant international interest in family-centred approaches, there is a dearth of research on operational experiences in implementation and scale-up. Our retrospective case study examined best practices and enabling factors during scale-up of family-centred care in ten health facilities and ten community clinics supported by a non-governmental organization, Mildmay, in Central Uganda. Methods included key informant interviews with programme management and families, and a desk review of hospital management information systems (HMIS) uptake data. In the 84 months following the scale-up of the family-centred approach in HIV care, Mildmay experienced a 50-fold increase of family units registered in HIV care, a 40-fold increase of children enrolled in HIV care, and nearly universal coverage of paediatric cotrimoxazole prophylaxis. The Mildmay experience emphasizes the importance of streamlining care to maximize paediatric capture. This includes integrated service provision, incentivizing care-seeking as a family, creating child-friendly service environments, and minimizing missed paediatric testing opportunities by institutionalizing early infant diagnosis and provider-initiated testing and counselling. Task-shifting towards nurse-led clinics with community outreach support enabled rapid scale-up, as did an active management structure that allowed for real-time review and corrective action. The Mildmay experience suggests that family-centred approaches are operationally feasible, produce strong coverage outcomes, and can be well-managed during rapid scale-up.

  19. 42 CFR 71.53 - Nonhuman primates.

    Science.gov (United States)

    2010-10-01

    ... nonhuman primates that is suspected of being yellow fever, monkeypox, or Marburg/Ebola disease. (3... member of their staff suspected of having an infectious disease acquired from nonhuman primates. (f) Disease control measures. Upon receipt of evidence of exposure of nonhuman primates to a communicable...

  20. Nonhuman Primate Positron Emission Tomography Neuroimaging in Drug Abuse Research

    Science.gov (United States)

    Murnane, Kevin Sean

    2011-01-01

    Positron emission tomography (PET) neuroimaging in nonhuman primates has led to significant advances in our current understanding of the neurobiology and treatment of stimulant addiction in humans. PET neuroimaging has defined the in vivo biodistribution and pharmacokinetics of abused drugs and related these findings to the time course of behavioral effects associated with their addictive properties. With novel radiotracers and enhanced resolution, PET neuroimaging techniques have also characterized in vivo drug interactions with specific protein targets in the brain, including neurotransmitter receptors and transporters. In vivo determinations of cerebral blood flow and metabolism have localized brain circuits implicated in the effects of abused drugs and drug-associated stimuli. Moreover, determinations of the predisposing factors to chronic drug use and long-term neurobiological consequences of chronic drug use, such as potential neurotoxicity, have led to novel insights regarding the pathology and treatment of drug addiction. However, similar approaches clearly need to be extended to drug classes other than stimulants. Although dopaminergic systems have been extensively studied, other neurotransmitter systems known to play a critical role in the pharmacological effects of abused drugs have been largely ignored in nonhuman primate PET neuroimaging. Finally, the study of brain activation with PET neuroimaging has been replaced in humans mostly by functional magnetic resonance imaging (fMRI). There has been some success in implementing pharmacological fMRI in awake nonhuman primates. Nevertheless, the unique versatility of PET imaging will continue to complement the systems-level strengths of fMRI, especially in the context of nonhuman primate drug abuse research. PMID:21317354

  1. Cutaneous thermoreceptors in primates and sub-primates.

    Science.gov (United States)

    Iggo, A

    1969-02-01

    1. Cutaneous thermoreceptors were examined electrophysiologically in primates (monkey, baboon) and in sub-primates (dog and rat) by recording from single units dissected from peripheral nerves.2. Thermal stimuli were delivered from thermodes in contact with the skin.3. Primate ;cold' receptors had spot-like receptive fields and were found in both hairy and glabrous skin. The conduction velocities of the axons ranged from 0.6 to 15.3 m/sec.4. The discharge from the primate receptors characteristically appeared in bursts with intervals of silence within the range temperatures of 18-40 degrees C. Static and dynamic sensitivity curves were established, with maxima about 30 degrees C.5. Cold receptors in the lip of the dog had maximal sensitivity at 31-37 degrees C. The axons were myelinated with conduction velocities less than 20 m/sec.6. ;Warm' receptors, with maximal sensitivity at 40 degrees C and non-myelinated axons, were abundant in the scrotal nerve of the rat. The ;cold' receptors had maximal responses at 23-28 degrees C.7. The ;spurious' thermoreceptor behaviour of slowly adapting mechanoreceptors is described and the way in which they may distort integrated potential records from whole nerves is analysed.

  2. Scaled-Up Production and Transport Applications of Graphitic Carbon Nanomaterials

    Science.gov (United States)

    Saviers, Kimberly R.

    Graphitic carbon nanomaterials enhance the performance of engineered systems for energy harvesting and storage. However, commercial availability remains largely cost-prohibitive due to technical barriers to mass production. This thesis examines both the scaled-up production and energy transport applications of graphitic materials. Cost driven-production of graphitic petals is developed, carbon nanotube array thermal interface materials enhance waste heat energy harvesting, and microsupercapacitors are visually examined using a new electroreflectance measurement method. Graphitic materials have previously been synthesized using batch-style processing methods with small sample sizes, limiting their commercial viability. In order to increase production throughput, a roll-to-roll radio-frequency plasma chemical vapor deposition method is employed to continuously deposit graphitic petals on carbon fiber tow. In consideration of a full production framework, efficient and informative characterization methods in the form of electrical resistance and electrochemical capacitance are highlighted. To co-optimize the functional characteristics of the material, the processing conditions are comprehensively varied using a data-driven predictive design of experiments method. Repeatable and reliable production of graphitic materials will enable a host of creative graphene-based devices to emerge into the marketplace. Two such applications are discussed in the remaining chapters. Waste heat is most efficiently harvested at high temperatures, such as vehicle exhaust systems near 600°C. However, the resistance to heat flux at the interfaces between the harvesting device and its surroundings is detrimental to the system-level performance. To study the performance of thermal interface materials up to 700°C, a reference bar measurement method was designed. Design considerations are discussed and compared to past implementations, particularly regarding radiation heat flux and thermal

  3. Pathogenesis of Varicelloviruses in primates

    Science.gov (United States)

    Ouwendijk, Werner J.D.; Verjans, Georges M.G.M.

    2014-01-01

    Varicelloviruses in primates comprise the prototypic human varicella-zoster virus (VZV) and its non-human primate homologue simian varicella virus (SVV). Both viruses cause varicella as a primary infection, establish latency in ganglionic neurons and reactivate later in life to cause herpes zoster in their respective hosts. VZV is endemic worldwide and although varicella is usually a benign disease in childhood, VZV reactivation is a significant cause of neurological disease in the elderly and in immunocompromised individuals. The pathogenesis of VZV infection remains ill-defined, mostly due to the species restriction of VZV that impedes studies in experimental animal models. SVV infection of non-human primates parallels virological, clinical, pathological and immunological features of human VZV infection, thereby providing an excellent model to study the pathogenesis of varicella and herpes zoster in its natural host. In this review, we discuss recent studies that provided novel insight in both the virus and host factors involved in the three elementary stages of Varicellovirus infection in primates: primary infection, latency and reactivation. PMID:25255989

  4. Pathogenesis of varicelloviruses in primates.

    Science.gov (United States)

    Ouwendijk, Werner J D; Verjans, Georges M G M

    2015-01-01

    Varicelloviruses in primates comprise the prototypic human varicella-zoster virus (VZV) and its non-human primate homologue, simian varicella virus (SVV). Both viruses cause varicella as a primary infection, establish latency in ganglionic neurons and reactivate later in life to cause herpes zoster in their respective hosts. VZV is endemic worldwide and, although varicella is usually a benign disease in childhood, VZV reactivation is a significant cause of neurological disease in the elderly and in immunocompromised individuals. The pathogenesis of VZV infection remains ill-defined, mostly due to the species restriction of VZV that impedes studies in experimental animal models. SVV infection of non-human primates parallels virological, clinical, pathological and immunological features of human VZV infection, thereby providing an excellent model to study the pathogenesis of varicella and herpes zoster in its natural host. In this review, we discuss recent studies that provided novel insight in both the virus and host factors involved in the three elementary stages of Varicellovirus infection in primates: primary infection, latency and reactivation. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  5. HIV scale-up in Mozambique: exceptionalism, normalisation and global health.

    Science.gov (United States)

    Høg, Erling

    2014-01-01

    The large-scale introduction of HIV and AIDS services in Mozambique from 2000 onwards occurred in the context of deep political commitment to sovereign nation-building and an important transition in the nation's health system. Simultaneously, the international community encountered a willing state partner that recognised the need to take action against the HIV epidemic. This article examines two critical policy shifts: sustained international funding and public health system integration (the move from parallel to integrated HIV services). The Mozambican government struggles to support its national health system against privatisation, NGO competition and internal brain drain. This is a sovereignty issue. However, the dominant discourse on self-determination shows a contradictory twist: it is part of the political rhetoric to keep the sovereignty discourse alive, while the real challenge is coordination, not partnerships. Nevertheless, we need more anthropological studies to understand the political implications of global health funding and governance. Other studies need to examine the consequences of public health system integration for the quality of access to health care.

  6. Two stage hydrolysis of corn stover at high solids content for mixing power saving and scale-up applications.

    Science.gov (United States)

    Liu, Ke; Zhang, Jian; Bao, Jie

    2015-11-01

    A two stage hydrolysis of corn stover was designed to solve the difficulties between sufficient mixing at high solids content and high power input encountered in large scale bioreactors. The process starts with the quick liquefaction to convert solid cellulose to liquid slurry with strong mixing in small reactors, then followed the comprehensive hydrolysis to complete saccharification into fermentable sugars in large reactors without agitation apparatus. 60% of the mixing energy consumption was saved by removing the mixing apparatus in large scale vessels. Scale-up ratio was small for the first step hydrolysis reactors because of the reduced reactor volume. For large saccharification reactors in the second step, the scale-up was easy because of no mixing mechanism was involved. This two stage hydrolysis is applicable for either simple hydrolysis or combined fermentation processes. The method provided a practical process option for industrial scale biorefinery processing of lignocellulose biomass. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Evaluation of ethanol production from corncob using Scheffersomyces (Pichia) stipitis CBS 6054 by volumetric scale-up

    Science.gov (United States)

    Jae-Won Lee; J.Y. Zhu; Danilo Scordia; Thomas W. Jeffries

    2011-01-01

    In scale-up, the potential of ethanol production by dilute sulfuric acid pretreatment using corncob was investigated. Pretreatments were performed at 170 °C with various acid concentrations ranging from 0% to 1.656% based on oven dry weight. Following pretreatment, pretreated biomass yield ranged from 59% to 67%. More than 90% of xylan was removed at 0.828% of sulfuric...

  8. Scaling up health promotion interventions in the era of HIV/AIDS: challenges for a rights based approach.

    Science.gov (United States)

    Chopra, Mickey; Ford, Neil

    2005-12-01

    A sustained scaled up response to global public health challenges such as HIV/AIDS will require a functioning and efficient health system, based on the foundation of strong primary health care. Whilst this is necessary, it is not sufficient. Health promotion strategies need to be put into place to better engage and support families and communities in preventing disease, optimize caring, creating the demand for services and holding service providers to account. There will have to be a move away from the traditional model whereby the problem of HIV/TB/malaria is to be solved by merely increasing resources to a centralized bureaucracy that tries to increase the supply of services including health promotion messages. Development projects and programs that succeed are based on understanding of local practice and preferences, rather than on internationally 'generalized models' of how people or villages should behave and what they should want. This paper will first briefly review different approaches to scaling up health promotion interventions, some of the key obstacles in scaling up and then suggest some possible solutions with a focus on a human rights based approach. This approach changes the emphasis from the content of the message to the characteristics of a community's organisations and institutions. Scaling up occurs as a process of association between state actors and civil society that is planned strategically and involves a sharing of experience and a strong learning process among the association partners. A human rights-based approach can facilitate such an approach through developing a common vision, delineating roles and responsibility and facilitating communication channels for the most vulnerable. But this will require health development agencies to pursue a more overt political agenda.

  9. Understanding the scaling-up of community energy niches through Strategic Niche Management Theory: insights from Finland

    OpenAIRE

    Ruggiero, Salvatore; Martiskainen, Mari; Onkila, Tiina

    2018-01-01

    The growing phenomenon of civil society involvement in renewable energy generation has attracted researchers’ interest. However, rather little is known of how a diverse and relatively small sector such as community energy could scale up and promote a change in energy production. We examine this issue through the lens of Strategic Niche Management (SNM) and conceptualize community energy as a socio-technical niche that holds the potential to promote a transition to renewable energy. Drawing on...

  10. Challenges and support for scaling up upcycling businesses in the UK: Insights from small-business entrepreneurs

    OpenAIRE

    Sung, Kyungeun; Cooper, Tim; Ramanathan, Usha; Singh, Jagdeep

    2017-01-01

    open access article Upcycling is the creation or modification of a product from used materials, components and products which is of equal or higher quality or value than the compositional elements. Within the context of increased product longevity, it enables a reduction in the use of raw materials by extending the lifetime of used materials, components and products, thereby increasing material efficiency and reducing industrial energy consumption. If scaled up to a considerable level thro...

  11. Scaling-up public sector childhood diarrhea management program: Lessons from Indian states of Gujarat, Uttar Pradesh and Bihar.

    Science.gov (United States)

    Kumar, Sanjeev; Roy, Rajashree; Dutta, Sucharita

    2015-12-01

    Diarrhea remains a leading cause of death among children under five in India. Public health sector is an important source for diarrhea treatment with oral rehydration salts (ORS) and zinc. In 2010, Micronutrient Initiative started a project to improve service delivery for childhood diarrhea management through public health sector in Gujarat, Uttar Pradesh (UP) and Bihar. This paper aims to highlight feasible strategies, experiences and lessons learned from scaling-up zinc and ORS for childhood diarrhea management in the public sector in three Indian states. The project was implemented in six districts of Gujarat, 12 districts of UP and 15 districts of Bihar, which includes 10.5 million children. Program strategies included capacity building of health care providers, expanding service delivery through community health workers (CHWs), providing supportive supervision to CHWs, ensuring supplies and conducting monitoring and evaluation. The lessons described in this paper are based on program data, government documents and studies that were used to generate evidence and inform program scale-up. 140 000 health personnel, including CHWs, were trained in childhood diarrhea management. During three years, CHWs had sustained knowledge and have treated and reported more than three million children aged 2-59 months having diarrhea, of which 84% were treated with both zinc and ORS. The successful strategies were scaled-up. It is feasible and viable to introduce and scale-up zinc and ORS for childhood diarrhea treatment through public sector. Community-based service delivery, timely and adequate supplies, trained staff and pro-active engagement with government were essential for program success.

  12. Constraints, synergies and avenues for scaling up breastfeeding, antibiotics for pneumonia and IMCI interventions in the Cusco region, Peru

    OpenAIRE

    Giselle Sarganas; Robert Scherpbier; Gericke, Christian A

    2012-01-01

    Objective: The purpose of this qualitative case study was to assess the feasibility of scaling up exclusive breastfeeding for 6 months, antibiotics for pneumonia and integrated management of childhood illness (IMCI) child interventions in three districts of the Cusco region, Peru. Methods: During field visits, constraints, synergies and solutions to the implementation of the selected interventions were collected through observational recording and interviews of mothers, health workers, and he...

  13. Scaling up of breastfeeding promotion programs in low- and middle-income countries: the "breastfeeding gear" model.

    Science.gov (United States)

    Pérez-Escamilla, Rafael; Curry, Leslie; Minhas, Dilpreet; Taylor, Lauren; Bradley, Elizabeth

    2012-11-01

    Breastfeeding (BF) promotion is one of the most cost-effective interventions to advance mother-child health. Evidence-based frameworks and models to promote the effective scale up and sustainability of BF programs are still lacking. A systematic review of peer-reviewed and gray literature reports was conducted to identify key barriers and facilitators for scale up of BF programs in low- and middle-income countries. The review identified BF programs located in 28 countries in Africa, Latin America and the Caribbean, and Asia. Study designs included case studies, qualitative studies, and observational quantitative studies. Only 1 randomized, controlled trial was identified. A total of 22 enabling factors and 15 barriers were mapped into a scale-up framework termed "AIDED" that was used to build the parsimonious breastfeeding gear model (BFGM). Analogous to a well-oiled engine, the BFGM indicates the need for several key "gears" to be working in synchrony and coordination. Evidence-based advocacy is needed to generate the necessary political will to enact legislation and policies to protect, promote, and support BF at the hospital and community levels. This political-policy axis in turn drives the resources needed to support workforce development, program delivery, and promotion. Research and evaluation are needed to sustain the decentralized program coordination "gear" required for goal setting and system feedback. The BFGM helps explain the different levels of performance in national BF outcomes in Mexico and Brazil. Empirical research is recommended to further test the usefulness of the AIDED framework and BFGM for global scaling up of BF programs.

  14. Voluntary medical male circumcision: strategies for meeting the human resource needs of scale-up in southern and eastern Africa.

    Directory of Open Access Journals (Sweden)

    Kelly Curran

    2011-11-01

    Full Text Available Voluntary medical male circumcision (VMMC reduces female-to-male HIV transmission by approximately 60%; modeling suggests that scaling up VMMC to 80% of men 15- to 49-years-old within five years would avert over 3.3 million new HIV infections in 14 high priority countries/regions in southern and eastern Africa by 2025 and would require 20.33 million circumcisions. However, the shortage of health professionals in these countries must be addressed to reach these proposed coverage levels. To identify human resource approaches that are being used to improve VMMC volume and efficiency, we looked at previous literature and conducted a program review. We identified surgical efficiencies, non-surgical efficiencies, task shifting, task sharing, temporary redeployment of public sector staff during VMMC campaign periods, expansion of the health workforce through recruitment of unemployed, recently retired, newly graduating, or on-leave health care workers, and the use of volunteer medical staff from other countries as approaches that address human resource constraints. Case studies from Kenya, Tanzania, and Swaziland illustrate several innovative responses to human resource challenges. Although the shortage of skilled personnel remains a major challenge to the rapid scale-up of VMMC in the 14 African priority countries/regions, health programs throughout the region may be able to replicate or adapt these approaches to scale up VMMC for public health impact.

  15. An effective and simplified scale-up strategy for acarbose fermentation based on the carbon source control.

    Science.gov (United States)

    Li, Kun-tai; Wie, Sai-jin; Huang, Lin; Cheng, Xin

    2012-02-01

    The scale-up strategy for acarbose fermentation by Actinoplanes sp. A56 was explored in this paper. The results obtained in shake-flask cultivation demonstrated that the ratio of maltose and glucose had significant effects on the biosynthesis of acarbose, and the feeding medium containing 3:1 (mass ratio) of maltose and glucose was favorable for acarbose production. Then the correlation of the carbon source concentration with acarbose production was further investigated in 100-l fermenter, and the results showed that 7.5-8.0 g of total sugar/100 ml and 4.0-4.5 g of reducing sugar/100 ml were optimal for acarbose production. Based on the results in 100-l fermenter, an effective and simplified scale-up strategy was successfully established for acarbose fermentation in a 30-m(3) fermenter, by using total sugar and reducing sugar as the scale-up parameter. As a result, 4,327 mg of acarbose/l was obtained at 168 h of fermentation.

  16. At-line process analytical technology (PAT) for more efficient scale up of biopharmaceutical microfiltration unit operations.

    Science.gov (United States)

    Watson, Douglas S; Kerchner, Kristi R; Gant, Sean S; Pedersen, Joseph W; Hamburger, James B; Ortigosa, Allison D; Potgieter, Thomas I

    2016-01-01

    Tangential flow microfiltration (MF) is a cost-effective and robust bioprocess separation technique, but successful full scale implementation is hindered by the empirical, trial-and-error nature of scale-up. We present an integrated approach leveraging at-line process analytical technology (PAT) and mass balance based modeling to de-risk MF scale-up. Chromatography-based PAT was employed to improve the consistency of an MF step that had been a bottleneck in the process used to manufacture a therapeutic protein. A 10-min reverse phase ultra high performance liquid chromatography (RP-UPLC) assay was developed to provide at-line monitoring of protein concentration. The method was successfully validated and method performance was comparable to previously validated methods. The PAT tool revealed areas of divergence from a mass balance-based model, highlighting specific opportunities for process improvement. Adjustment of appropriate process controls led to improved operability and significantly increased yield, providing a successful example of PAT deployment in the downstream purification of a therapeutic protein. The general approach presented here should be broadly applicable to reduce risk during scale-up of filtration processes and should be suitable for feed-forward and feed-back process control. © 2015 American Institute of Chemical Engineers.

  17. Up-scaling expectations among Pakistan's HIV bureaucrats: entrepreneurs of the self and job precariousness post-scale-up.

    Science.gov (United States)

    Qureshi, Ayaz

    2014-01-01

    Existing research has documented how the expansion of HIV programming has produced new subjectivities among the recipients of interventions. However, this paper contends that changes in politics, power and subjectivities may also be seen among the HIV bureaucracy in the decade of scale-up. One year's ethnographic fieldwork was conducted among AIDS control officials in Pakistan at a moment of rolling back a World Bank-financed Enhanced Programme. In 2003, the World Bank convinced the Musharraf regime to scale up the HIV response, offering a multimillion dollar soft loan package. I explore how the Enhanced Programme initiated government employees into a new transient work culture and turned the AIDS control programmes into a hybrid bureaucracy. However, the donor money did not last long and individuals' entrepreneurial abilities were tested in a time of crisis engendered by dependence on aid, leaving them precariously exposed to job insecurity, and undermining the continuity of AIDS prevention and treatment in the country. I do not offer a story of global 'best practices' thwarted by local 'lack of capacity', but an ethnographic critique of the transnational HIV apparatus and its neoliberal underpinning. I suggest that this Pakistan-derived analysis is more widely relevant in the post-scale-up decade.

  18. Process scale-up considerations for non-thermal atmospheric-pressure plasma synthesis of nanoparticles by homogenous nucleation

    Science.gov (United States)

    Cole, Jonathan; Zhang, Yao; Liu, Tianqi; Liu, Chang-jun; Mohan Sankaran, R.

    2017-08-01

    Scale-up of non-thermal atmospheric-pressure plasma reactors for the synthesis of nanoparticles by homogeneous nucleation is challenging because the active volume is typically reduced to facilitate gas breakdown, enhance discharge stability, and limit particle size and agglomeration, but thus limits throughput. Here, we introduce a dielectric barrier discharge reactor consisting of a coaxial electrode geometry for nanoparticle production that enables a simple scale-up strategy whereby increasing the outer and inner electrode diameters, the plasma volume is increased approximately linearly, while maintaining a sufficiently small electrode gap to maintain the electric field strength. We show with two test reactors that for a given residence time, the nanoparticle production rate increases linearly with volume over a range of precursor concentrations, while having minimal effect on the shape of the particle size distribution. However, our study also reveals that increasing the total gas flow rate in a smaller volume reactor leads to an enhancement of precursor conversion and a comparable production rate to a larger volume reactor. These results suggest that scale-up requires better understanding of the influence of reactor geometry on particle growth dynamics and may not always be a simple function of reactor volume.

  19. Transgenic nonhuman primates for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Chan Anthony WS

    2004-06-01

    Full Text Available Abstract Animal models that represent human diseases constitute an important tool in understanding the pathogenesis of the diseases, and in developing effective therapies. Neurodegenerative diseases are complex disorders involving neuropathologic and psychiatric alterations. Although transgenic and knock-in mouse models of Alzheimer's disease, (AD, Parkinson's disease (PD and Huntington's disease (HD have been created, limited representation in clinical aspects has been recognized and the rodent models lack true neurodegeneration. Chemical induction of HD and PD in nonhuman primates (NHP has been reported, however, the role of intrinsic genetic factors in the development of the diseases is indeterminable. Nonhuman primates closely parallel humans with regard to genetic, neuroanatomic, and cognitive/behavioral characteristics. Accordingly, the development of NHP models for neurodegenerative diseases holds greater promise for success in the discovery of diagnoses, treatments, and cures than approaches using other animal species. Therefore, a transgenic NHP carrying a mutant gene similar to that of patients will help to clarify our understanding of disease onset and progression. Additionally, monitoring disease onset and development in the transgenic NHP by high resolution brain imaging technology such as MRI, and behavioral and cognitive testing can all be carried out simultaneously in the NHP but not in other animal models. Moreover, because of the similarity in motor repertoire between NHPs and humans, it will also be possible to compare the neurologic syndrome observed in the NHP model to that in patients. Understanding the correlation between genetic defects and physiologic changes (e.g. oxidative damage will lead to a better understanding of disease progression and the development of patient treatments, medications and preventive approaches for high risk individuals. The impact of the transgenic NHP model in understanding the role which

  20. Reward mechanisms in the brain and their role in dependence : evidence from neurophysiological and neuroimaging studies

    NARCIS (Netherlands)

    Martin-Soelch, C; Leenders, KL; Chevalley, AF; Missimer, J; Kunig, G; Magyar, S; Mino, A; Schultz, W

    2001-01-01

    This article reviews neuronal activity related to reward processing in primate and human brains. In the primate brain, neurophysiological methods provide a differentiated view of reward processing in a limited number of brain structures. Dopamine neurons respond to unpredictable rewards and produce

  1. Visuomotor cerebellum in human and nonhuman primates.

    Science.gov (United States)

    Voogd, Jan; Schraa-Tam, Caroline K L; van der Geest, Jos N; De Zeeuw, Chris I

    2012-06-01

    In this paper, we will review the anatomical components of the visuomotor cerebellum in human and, where possible, in non-human primates and discuss their function in relation to those of extracerebellar visuomotor regions with which they are connected. The floccular lobe, the dorsal paraflocculus, the oculomotor vermis, the uvula-nodulus, and the ansiform lobule are more or less independent components of the visuomotor cerebellum that are involved in different corticocerebellar and/or brain stem olivocerebellar loops. The floccular lobe and the oculomotor vermis share different mossy fiber inputs from the brain stem; the dorsal paraflocculus and the ansiform lobule receive corticopontine mossy fibers from postrolandic visual areas and the frontal eye fields, respectively. Of the visuomotor functions of the cerebellum, the vestibulo-ocular reflex is controlled by the floccular lobe; saccadic eye movements are controlled by the oculomotor vermis and ansiform lobule, while control of smooth pursuit involves all these cerebellar visuomotor regions. Functional imaging studies in humans further emphasize cerebellar involvement in visual reflexive eye movements and are discussed.

  2. A process evaluation of the scale up of a youth-friendly health services initiative in northern Tanzania

    Directory of Open Access Journals (Sweden)

    Renju Jenny

    2010-08-01

    Full Text Available Abstract Background While there are a number of examples of successful small-scale, youth-friendly services interventions aimed at improving reproductive health service provision for young people, these projects are often short term and have low coverage. In order to have a significant, long-term impact, these initiatives must be implemented over a sustained period and on a large scale. We conducted a process evaluation of the 10-fold scale up of an evaluated youth-friendly services intervention in Mwanza Region, Tanzania, in order to identify key facilitating and inhibitory factors from both user and provider perspectives. Methods The intervention was scaled up in two training rounds lasting six and 10 months. This process was evaluated through the triangulation of multiple methods: (i a simulated patient study; (ii focus group discussions and semi-structured interviews with health workers and trainers; (iii training observations; and (iv pre- and post-training questionnaires. These methods were used to compare pre- and post-intervention groups and assess differences between the two training rounds. Results Between 2004 and 2007, local government officials trained 429 health workers. The training was well implemented and over time, trainers' confidence and ability to lead sessions improved. The district-led training significantly improved knowledge relating to HIV/AIDS and puberty (RR ranged from 1.06 to 2.0, attitudes towards condoms, confidentiality and young people's right to treatment (RR range: 1.23-1.36. Intervention health units scored higher in the family planning and condom request simulated patient scenarios, but lower in the sexually transmitted infection scenario than the control health units. The scale up faced challenges in the selection and retention of trained health workers and was limited by various contextual factors and structural constraints. Conclusions Youth-friendly services interventions can remain well delivered, even

  3. Characterization of [11C]Cimbi-36 as an agonist PET radioligand for the 5-HT2A and 5-HT2C receptors in the nonhuman primate brain

    DEFF Research Database (Denmark)

    Finnema, Sjoerd J; Stepanov, Vladimir; Ettrup, Anders

    2014-01-01

    injection of [(11)C]Cimbi-36 the regional distribution of radioactivity in brain was in accordance with the known 5-HT2 receptor distribution. The two-tissue compartment model was superior for the description of the time-radioactivity curves of all examined brain regions. BPND values obtained with reference...

  4. Primate Experiments on SLS-1

    Science.gov (United States)

    Aochi, J.

    1985-01-01

    Experiments to study how certain body systems are affected by the space environment are described. These experiments are to be conducted on space shuttle flights. How weightlessness affects two body systems of primates are the prime concern. Thermoregulation and fluid and electrolyte homeostasis are the two systems concerned. The thermoregulation project will provide data on how body temperature and circadian rhythms are affected in a weightlessness environment and the homeostasis in fluids and electrolyte levels will address the problem of body fluid shifts.

  5. Assessing Anxiety in Nonhuman Primates

    Science.gov (United States)

    Coleman, Kristine; Pierre, Peter J.

    2014-01-01

    Anxiety can be broadly described as a psychological state in which normally innocuous environmental stimuli trigger negative emotional expectations. Human anxiety disorders are multidimensional and may be organic or acquired, situational or pervasive. The broad ranging nature of the anxiety phenotype speaks to the need for models that identify its various components and root causes to develop effective clinical treatments. The cross-species comparative approach to modeling anxiety disorders in animals aims to understand mechanisms that both contribute to and modulate anxiety. Nonhuman primate models provide an important bridge from nonprimate model systems because of the complexity of nonhuman primates’ biobehavioral capacities and their commonalities with human emotion. The broad goal of this review is to provide an overview of various procedures available to study anxiety in the nonhuman primate, with a focus on the behavioral aspects of anxiety. Commonly used methods covered in this review include assessing animals in their home environment or in response to an ethologically relevant threat, associative conditioning and startle response tests, and cognitive bias tests. We also discuss how these procedures can help veterinarians and researchers care for captive nonhuman primates. PMID:25225310

  6. ADVANCING THE FUNDAMENTAL UNDERSTANDING AND SCALE-UP OF TRISO FUEL COATERS VIA ADVANCED MEASUREMENT AND COMPUTATIONAL TECHNIQUES

    Energy Technology Data Exchange (ETDEWEB)

    Biswas, Pratim; Al-Dahhan, Muthanna

    2012-11-01

    Tri-isotropic (TRISO) fuel particle coating is critical for the future use of nuclear energy produced byadvanced gas reactors (AGRs). The fuel kernels are coated using chemical vapor deposition in a spouted fluidized bed. The challenges encountered in operating TRISO fuel coaters are due to the fact that in modern AGRs, such as High Temperature Gas Reactors (HTGRs), the acceptable level of defective/failed coated particles is essentially zero. This specification requires processes that produce coated spherical particles with even coatings having extremely low defect fractions. Unfortunately, the scale-up and design of the current processes and coaters have been based on empirical approaches and are operated as black boxes. Hence, a voluminous amount of experimental development and trial and error work has been conducted. It has been clearly demonstrated that the quality of the coating applied to the fuel kernels is impacted by the hydrodynamics, solids flow field, and flow regime characteristics of the spouted bed coaters, which themselves are influenced by design parameters and operating variables. Further complicating the outlook for future fuel-coating technology and nuclear energy production is the fact that a variety of new concepts will involve fuel kernels of different sizes and with compositions of different densities. Therefore, without a fundamental understanding the underlying phenomena of the spouted bed TRISO coater, a significant amount of effort is required for production of each type of particle with a significant risk of not meeting the specifications. This difficulty will significantly and negatively impact the applications of AGRs for power generation and cause further challenges to them as an alternative source of commercial energy production. Accordingly, the proposed work seeks to overcome such hurdles and advance the scale-up, design, and performance of TRISO fuel particle spouted bed coaters. The overall objectives of the proposed work are

  7. Antiretroviral treatment and the health workforce in South Africa: how have ART workers been affected by scaling up?

    Science.gov (United States)

    Tobi, Patrick; George, Gavin; Schmidt, Elena; Renton, Adrian

    2008-12-01

    To investigate the effect of scaling up antiretroviral treatment (ART) on the working environment and motivation of health workers in South Africa; and to suggest strategies to minimize negative effects and maximise positive effects. Exploratory interviews with health managers and senior clinical staff were used to identify locally relevant work environment indicators. A self-reported Likert scale questionnaire was administered to a randomly selected cohort of 269 health professionals at health facilities in KwaZulu Natal and Western Cape provinces of South Africa that included ART delivery sites. The cohort was disaggregated into ART and non-ART groups and differences between the two compared with Fisher's exact test and the non-parametric Mann-Whitney U-test. The ART sub-cohort reported: (i) a lighter workload (P = 0.013), (ii) higher level of staffing (P = 0.010), (iii) lower sickness absence (P = 0.032), (iv) higher overall job satisfaction (P = 0.010), (v) poorer physical state of their work premises (P = 0.003), and (vi) higher staff turnover (P = 0.036). Conclusion Scale-up affects the work environment in ways that influence workers' motivation both positively and negatively. A net negative balance is likely to drive staff out-migration, undermine the quality of care and compromise the capacity of the programme to achieve significant scale. As health workers are the most important element of the health system, a comprehensive and systematic understanding of scale-up impacts on their working conditions and motivation needs to be an integral part of any delivery strategy.

  8. Population size estimation of men who have sex with men through the network scale-up method in Japan.

    Directory of Open Access Journals (Sweden)

    Satoshi Ezoe

    Full Text Available BACKGROUND: Men who have sex with men (MSM are one of the groups most at risk for HIV infection in Japan. However, size estimates of MSM populations have not been conducted with sufficient frequency and rigor because of the difficulty, high cost and stigma associated with reaching such populations. This study examined an innovative and simple method for estimating the size of the MSM population in Japan. We combined an internet survey with the network scale-up method, a social network method for estimating the size of hard-to-reach populations, for the first time in Japan. METHODS AND FINDINGS: An internet survey was conducted among 1,500 internet users who registered with a nationwide internet-research agency. The survey participants were asked how many members of particular groups with known population sizes (firepersons, police officers, and military personnel they knew as acquaintances. The participants were also asked to identify the number of their acquaintances whom they understood to be MSM. Using these survey results with the network scale-up method, the personal network size and MSM population size were estimated. The personal network size was estimated to be 363.5 regardless of the sex of the acquaintances and 174.0 for only male acquaintances. The estimated MSM prevalence among the total male population in Japan was 0.0402% without adjustment, and 2.87% after adjusting for the transmission error of MSM. CONCLUSIONS: The estimated personal network size and MSM prevalence seen in this study were comparable to those from previous survey results based on the direct-estimation method. Estimating population sizes through combining an internet survey with the network scale-up method appeared to be an effective method from the perspectives of rapidity, simplicity, and low cost as compared with more-conventional methods.

  9. Scaling-up a public health innovation: a comparative study of post-abortion care in Bolivia and Mexico.

    Science.gov (United States)

    Billings, Deborah L; Crane, Barbara B; Benson, Janie; Solo, Julie; Fetters, Tamara

    2007-06-01

    Post-abortion care (PAC), an innovation for treating women with complications of unsafe abortion, has been introduced in public health systems around the world since the 1994 International Conference on Population and Development (ICPD). This article analyzes the process of scaling-up two of the three key elements of the original PAC model: providing prompt clinical treatment to women with abortion complications and offering post-abortion contraceptive counseling and methods in Bolivia and Mexico. The conceptual framework developed from this comparative analysis includes the environmental context for PAC scale-up; the major influences on start-up, expansion, and institutionalization of PAC; and the health, financial, and social impacts of institutionalization. Start-up in both Bolivia and Mexico was facilitated by innovative leaders or catalyzers who were committed to introducing PAC services into public health care settings, collaboration between international organizations and public health institutions, and financial resources. Important processes for successful PAC expansion included strengthening political commitment to PAC services through research, advocacy, and partnerships; improving health system capacity through training, supervision, and development of service guidelines; and facilitating health system access to essential technologies. Institutionalization of PAC has been more successful in Bolivia than Mexico, as measured by a series of proposed indicators. The positive health and financial impacts of PAC institutionalization have been partially measured in Bolivia and Mexico. Other hypotheses--that scaling-up PAC will significantly reduce maternal mortality and morbidity, decrease abortion-related stigma, and prepare the way for efforts to reform restrictive abortion laws and policies--have yet to be tested.

  10. The BeUpstanding ProgramTM: Scaling up the Stand Up Australia Workplace Intervention for Translation into Practice

    Directory of Open Access Journals (Sweden)

    Genevieve N Healy

    2016-05-01

    Full Text Available Context and purpose: Too much sitting is now recognised as a common risk factor for several health outcomes, with the workplace identified as a key setting in which to address prolonged sitting time. The Stand Up Australia intervention was designed to reduce prolonged sitting in the workplace by addressing influences at multiple-levels, including the organisation, the environment, and the individual. Intervention success has been achieved within the context of randomised controlled trials, where research staff deliver several of the key intervention components. This study describes the initial step in the multi-phase process of scaling up the Stand Up Australia intervention for workplace translation. Methods: A research-government partnership was critical in funding and informing the prototype for the scaled up BeUpstanding programTM. Evidence, protocols and materials from Stand Up Australia were adapted in collaboration with funding partner Workplace Health and Safety Queensland to ensure consistency and compatibility with existing government frameworks and resources. In recognition of the key role of workplace champions in facilitating workplace health promotion programs, the BeUpstanding programTM is designed to be delivered through a stand-alone, free, website-based toolkit using a 'train the champion' approach. Key findings and significance: The BeUpstanding programTM was influenced by the increasing recognition of prolonged sitting as an emerging health issue as well as industry demand. The research-government partnership was critical in informing and resourcing the development of the scaled-up program.

  11. Scale up of a Plasmodium falciparum elimination program and surveillance system in Kayin State, Myanmar [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Daniel M. Parker

    2017-12-01

    Full Text Available Background: Myanmar has one of the largest malaria burdens in the Greater Mekong Subregion (GMS. Throughout the GMS, Plasmodium falciparum parasites are increasingly resistant to artemisinin combination therapies. Given that there are no current alternative treatment therapies, one proposed solution to the threat of untreatable P. falciparum malaria is to eliminate the parasite from the region. Several small-scale elimination projects have been piloted in the GMS, including along the Myanmar-Thailand border. Following the success of the pilot elimination project along the Myanmar-Thailand border, there was a scale up to a broad area of Eastern Kayin State, Myanmar. Here we describe the establishment of the scale up elimination project in Easter Kayin State. Methods: The scale up relied on geographic reconnaissance and a geographic information system, community engagement, generalized access to community-based early diagnosis and treatment, near real-time epidemiological surveillance, cross sectional malaria prevalence surveys and targeted mass drug administration in villages with high prevalence of P. falciparum malaria. Molecular markers of drug resistance were also monitored in individuals with symptomatic and asymptomatic infections. Discussion: This protocol illustrates the establishment of an elimination project and operational research in a remote, rural area encompassing several armed groups, multiple political organizations and a near-absent health care infrastructure. The establishment of the project relied on a strong rapport with the target community, on-the-ground knowledge (through geographic surveys and community engagement, rapid decision making and an approach that was flexible enough to quickly adapt to a complex landscape. The elimination project is ongoing, now over three years in operation, and assessment of the impact of this operational research will follow. This project has relevance not only for other malaria elimination

  12. Bioprocess integration for human mesenchymal stem cells: From up to downstream processing scale-up to cell proteome characterization.

    Science.gov (United States)

    Cunha, Bárbara; Aguiar, Tiago; Carvalho, Sofia B; Silva, Marta M; Gomes, Ricardo A; Carrondo, Manuel J T; Gomes-Alves, Patrícia; Peixoto, Cristina; Serra, Margarida; Alves, Paula M

    2017-04-20

    To deliver the required cell numbers and doses to therapy, scaling-up production and purification processes (at least to the liter-scale) while maintaining cells' characteristics is compulsory. Therefore, the aim of this work was to prove scalability of an integrated streamlined bioprocess compatible with current good manufacturing practices (cGMP) comprised by cell expansion, harvesting and volume reduction unit operations using human mesenchymal stem cells (hMSC) isolated from bone marrow (BM-MSC) and adipose tissue (AT-MSC). BM-MSC and AT-MSC expansion and harvesting steps were scaled-up from spinner flasks to 2L scale stirred tank single-use bioreactor using synthetic microcarriers and xeno-free medium, ensuring high cellular volumetric productivities (50×106cellL-1day-1), expansion factors (14-16 fold) and cell recovery yields (80%). For the concentration step, flat sheet cassettes (FSC) and hollow fiber cartridges (HF) were compared showing a fairly linear scale-up, with a need to slightly decrease the permeate flux (30-50 LMH, respectively) to maximize cell recovery yield. Nonetheless, FSC allowed to recover 18% more cells after a volume reduction factor of 50. Overall, at the end of the entire bioprocess more than 65% of viable (>95%) hMSC could be recovered without compromising cell's critical quality attributes (CQA) of viability, identity and differentiation potential. Alongside the standard quality assays, a proteomics workflow based on mass spectrometry tools was established to characterize the impact of processing on hMSC's CQA; These analytical tools constitute a powerful tool to be used in process design and development. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Development of an inexpensive, low attenuation styrofoam primate chair for use in a PET scanner

    NARCIS (Netherlands)

    Kortekaas, R; van Waarde, A; Maguire, RP; Leenders, KL; Elsinga, PH

    Pharmacokinetic modelling of radiotracers for positron emission tomography (PET) imaging of neuroreceptors can be performed with time-activity data for brain and blood. We aimed to develop an alternative to withdrawal of arterial blood samples for acquisition of a blood curve. A supportive primate

  14. Basic neuroscience research with nonhuman primates: a small but indispensable component of biomedical research

    NARCIS (Netherlands)

    Roelfsema, Pieter R.; Treue, Stefan

    2014-01-01

    Research with nonhuman primates represents a small component of neuroscience with far-reaching relevance that is irreplaceable for essential insights into cognitive functions, brain disease, and therapy. Transparency and widespread information about this research and its importance is central to

  15. Basic neuroscience research with nonhuman primates : a small but indispensable component of biomedical research

    NARCIS (Netherlands)

    Roelfsema, Pieter R; Treue, Stefan

    2014-01-01

    Research with nonhuman primates represents a small component of neuroscience with far-reaching relevance that is irreplaceable for essential insights into cognitive functions, brain disease, and therapy. Transparency and widespread information about this research and its importance is central to

  16. Scaling up watershed model parameters: flow and load simulations of the Edisto River Basin, South Carolina, 2007-09

    Science.gov (United States)

    Feaster, Toby D.; Benedict, Stephen T.; Clark, Jimmy M.; Bradley, Paul M.; Conrads, Paul

    2014-01-01

    As part of an ongoing effort by the U.S. Geological Survey to expand the understanding of relations among hydrologic, geochemical, and ecological processes that affect fish-tissue mercury concentrations within the Edisto River Basin, analyses and simulations of the hydrology of the Edisto River Basin were made using the topography-based hydrological model (TOPMODEL). A primary focus of the investigation was to assess the potential for scaling up a previous application of TOPMODEL for the McTier Creek watershed, which is a small headwater catchment to the Edisto River Basin. Scaling up was done in a step-wise manner, beginning with applying the calibration parameters, meteorological data, and topographic-wetness-index data from the McTier Creek TOPMODEL to the Edisto River TOPMODEL. Additional changes were made for subsequent simulations, culminating in the best simulation, which included meteorological and topographic wetness index data from the Edisto River Basin and updated calibration parameters for some of the TOPMODEL calibration parameters. The scaling-up process resulted in nine simulations being made. Simulation 7 best matched the streamflows at station 02175000, Edisto River near Givhans, SC, which was the downstream limit for the TOPMODEL setup, and was obtained by adjusting the scaling factor, including streamflow routing, and using NEXRAD precipitation data for the Edisto River Basin. The Nash-Sutcliffe coefficient of model-fit efficiency and Pearson’s correlation coefficient for simulation 7 were 0.78 and 0.89, respectively. Comparison of goodness-of-fit statistics between measured and simulated daily mean streamflow for the McTier Creek and Edisto River models showed that with calibration, the Edisto River TOPMODEL produced slightly better results than the McTier Creek model, despite the substantial difference in the drainage-area size at the outlet locations for the two models (30.7 and 2,725 square miles, respectively). Along with the TOPMODEL

  17. Biogas potential of high strength municipal wastewater treatment in laboratory scale up-flow anaerobic slugde blanket (UASB) reactors

    OpenAIRE

    Safitri, Anissa Sukma

    2016-01-01

    The main focus of this study is investigating the effectiveness of anaerobic treatment of municipal wastewater for converting organic matter to methane production in anaerobic granular sludge reactors. In-house designed laboratory scale, up-flow anaerobic sludge blanket (UASB) reactor systems were set up for treating of high strength municipal wastewater treatment i.e. below 1200 mg COD/l under mesophilic condition (20 – 25 °C). Three UASB reactors were set up in the study; one reactor (React...

  18. Membrane-aerated biofilms for high rate biotreatment: performance appraisal, engineering principles, scale-up, and development requirements.

    Science.gov (United States)

    Syron, Eoin; Casey, Eoin

    2008-03-15

    Diffusion of the electron acceptor is the rate controlling step in virtually all biofilm reactors employed for aerobic wastewater treatment. The membrane-aerated biofilm reactor (MABR) is a technology that can deliver oxygen at high rates and transfer efficiencies, thereby enhancing the biofilm activity. This paper provides a comparative performance rate analysis of the MABR in terms of its application for carbonaceous pollutant removal, nitrification/denitrification and xenobiotic biotreatment. We also describe the mechanisms influencing process performance in the MABR and the inter-relationships between these factors. The challenges involved in scaling-up the process are discussed with recommendations for prioritization of research needs.

  19. Application of twin screw extrusion to the manufacture of cocrystals: scale-up of AMG 517-sorbic acid cocrystal production.

    Science.gov (United States)

    Daurio, Dominick; Nagapudi, Karthik; Li, Lan; Quan, Peter; Nunez, Fernando-Alvarez

    2014-01-01

    The application of twin screw extrusion (TSE) in the scale-up of cocrystal production was investigated by using AMG 517-sorbic acid as a model system. Extrusion parameters that influenced conversion to the cocrystal such as temperature, feed rate and screw speed were investigated. Extent of conversion to the cocrystal was found to have a strong dependence on temperature and a moderate dependence on feed rate and screw speed. Cocrystals made by the TSE process were found to have superior mechanical properties than solution grown cocrystals. Additionally, moving to a TSE process eliminated the need for solvent.

  20. Scaling up a School-Based Sexual and Reproductive Health Intervention in Rural Tanzania: A Process Evaluation Describing the Implementation Realities for the Teachers

    Science.gov (United States)

    Renju, Jenny; Nyalali, Kija; Andrew, Bahati; Kishamawe, Coleman; Kimaryo, Micheal; Remes, Pieter; Changalucha, John; Obasi, Angela

    2010-01-01

    Little is known about the nature and mechanisms of factors that facilitate or inhibit the scale-up and subsequent implementation of school-based adolescent sexual and reproductive health (ASRH) interventions. We present process evaluation findings examining the factors that affected the 10-fold scale-up of such an intervention, focussing on…

  1. A SCALE-UP Mock-Up: Comparison of Student Learning Gains in High- and Low-Tech Active-Learning Environments

    Science.gov (United States)

    Soneral, Paula A. G.; Wyse, Sara A.

    2017-01-01

    Student-centered learning environments with upside-down pedagogies (SCALE-UP) are widely implemented at institutions across the country, and learning gains from these classrooms have been well documented. This study investigates the specific design feature(s) of the SCALE-UP classroom most conducive to teaching and learning. Using pilot survey…

  2. Identifying the Characteristics of Effective High Schools: Report from Year One of the National Center on Scaling up Effective Schools. Research Report

    Science.gov (United States)

    Rutledge, Stacey; Cohen-Vogel, Lora; Osborne-Lampkin, La'Tara

    2012-01-01

    The National Center on Scaling up Effective Schools (NCSU) is a five-year project working to develop, implement, and test new processes to scale up effective practices in high schools that districts will be able to apply within the context of their own unique goals and circumstances. This report describes the activities and findings of the first…

  3. Cognitive consilience: Primate non-primary neuroanatomical circuits underlying cognition

    Directory of Open Access Journals (Sweden)

    Soren Van Hout Solari

    2011-12-01

    Full Text Available Interactions between the cerebral cortex, thalamus, and basal ganglia form the basis ofcognitive information processing in the mammalian brain. Understanding the principles ofneuroanatomical organization in these structures is critical to understanding the functions theyperform and ultimately how the human brain works. We have manually distilled and synthesizedhundreds of primate neuroanatomy facts into a single interactive visualization. The resultingpicture represents the fundamental neuroanatomical blueprint upon which cognitive functionsmust be implemented. Within this framework we hypothesize and detail 7 functional circuitscorresponding to psychological perspectives on the brain: consolidated long-term declarativememory, short-term declarative memory, working memory/information processing, behavioralmemory selection, behavioral memory output, cognitive control, and cortical information flow regulation. Each circuit is described in terms of distinguishable neuronal groups including thecerebral isocortex (9 pyramidal neuronal groups, parahippocampal gyrus and hippocampus,thalamus (4 neuronal groups, basal ganglia (7 neuronal groups, metencephalon, basal forebrainand other subcortical nuclei. We focus on neuroanatomy related to primate non-primary corticalsystems to elucidate the basis underlying the distinct homotypical cognitive architecture. To dis-play the breadth of this review, we introduce a novel method of integrating and presenting datain multiple independent visualizations: an interactive website (www.cognitiveconsilience.comand standalone iPhone and iPad applications. With these tools we present a unique, annotatedview of neuroanatomical consilience (integration of knowledge.

  4. The success factors of scaling-up Estonian sexual and reproductive health youth clinic network--from a grassroots initiative to a national programme 1991-2013.

    Science.gov (United States)

    Kempers, Jari; Ketting, Evert; Chandra-Mouli, Venkatraman; Raudsepp, Triin

    2015-01-08

    A growing number of middle-income countries are scaling up youth-friendly sexual and reproductive health pilot projects to national level programmes. Yet, there are few case studies on successful national level scale-up of such programmes. Estonia is an excellent example of scale-up of a small grassroots adolescent sexual and reproductive health initiative to a national programme, which most likely contributed to improved adolescent sexual and reproductive health outcomes. This study; (1) documents the scale-up process of the Estonian youth clinic network 1991-2013, and (2) analyses factors that contributed to the successful scale-up. This research provides policy makers and programme managers with new insights to success factors of the scale-up, that can be used to support planning, implementation and scale-up of adolescent sexual and reproductive health programmes in other countries. Information on the scale-up process and success factors were collected by conducting a literature review and interviewing key stakeholders. The findings were analysed using the WHO-ExpandNet framework, which provides a step-by-step process approach for design, implementation and assessment of the results of scaling-up health innovations. The scale-up was divided into two main phases: (1) planning the scale-up strategy 1991-1995 and (2) managing the scaling-up 1996-2013. The planning phase analysed innovation, user organizations (youth clinics), environment and resource team (a national NGO and international assistance). The managing phase examines strategic choices, advocacy, organization, resource mobilization, monitoring and evaluation, strategic planning and management of the scale-up. The main factors that contributed to the successful scale-up in Estonia were: (1) favourable social and political climate, (2) clear demonstrated need for the adolescent services, (3) a national professional organization that advocated, coordinated and represented the youth clinics, (4) enthusiasm

  5. Lutein and Brain Function

    Directory of Open Access Journals (Sweden)

    John W. Erdman

    2015-10-01

    Full Text Available Lutein is one of the most prevalent carotenoids in nature and in the human diet. Together with zeaxanthin, it is highly concentrated as macular pigment in the foveal retina of primates, attenuating blue light exposure, providing protection from photo-oxidation and enhancing visual performance. Recently, interest in lutein has expanded beyond the retina to its possible contributions to brain development and function. Only primates accumulate lutein within the brain, but little is known about its distribution or physiological role. Our team has begun to utilize the rhesus macaque (Macaca mulatta model to study the uptake and bio-localization of lutein in the brain. Our overall goal has been to assess the association of lutein localization with brain function. In this review, we will first cover the evolution of the non-human primate model for lutein and brain studies, discuss prior association studies of lutein with retina and brain function, and review approaches that can be used to localize brain lutein. We also describe our approach to the biosynthesis of 13C-lutein, which will allow investigation of lutein flux, localization, metabolism and pharmacokinetics. Lastly, we describe potential future research opportunities.

  6. Extraction of bioactives from Orthosiphon stamineus using microwave and ultrasound-assisted techniques: Process optimization and scale up.

    Science.gov (United States)

    Chan, Chung-Hung; See, Tiam-You; Yusoff, Rozita; Ngoh, Gek-Cheng; Kow, Kien-Woh

    2017-04-15

    This work demonstrated the optimization and scale up of microwave-assisted extraction (MAE) and ultrasonic-assisted extraction (UAE) of bioactive compounds from Orthosiphon stamineus using energy-based parameters such as absorbed power density and absorbed energy density (APD-AED) and response surface methodology (RSM). The intensive optimum conditions of MAE obtained at 80% EtOH, 50mL/g, APD of 0.35W/mL, AED of 250J/mL can be used to determine the optimum conditions of the scale-dependent parameters i.e. microwave power and treatment time at various extraction scales (100-300mL solvent loading). The yields of the up scaled conditions were consistent with less than 8% discrepancy and they were about 91-98% of the Soxhlet extraction yield. By adapting APD-AED method in the case of UAE, the intensive optimum conditions of the extraction, i.e. 70% EtOH, 30mL/g, APD of 0.22W/mL, AED of 450J/mL are able to achieve similar scale up results. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. FatMan vs. LittleBoy: Scaling up Linear Algebraic Operations in Scale-out Data Platforms

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Seung-Hwan [ORNL; Xu, Luna [Virginia Tech, Blacksburg, VA; Butt, Ali R [Virginia Tech, Blacksburg, VA; Sukumar, Sreenivas Rangan [ORNL; Kannan, Ramakrishnan [ORNL

    2016-01-01

    Linear algebraic operations such as matrix manipulations form the kernel of many machine learning and other crucial algorithms. Scaling up as well as scaling out such algorithms are highly desirable to enable efficient processing over millions of data points. To this end, we present a matrix manipulation approach to effectively scale-up each node in a scale-out data parallel platform such as Apache Spark. Specifically, we enable hardware acceleration for matrix multiplications in a distributed Spark setup without user intervention. Our approach supports both dense and sparse distributed matrices, and provides flexible control of acceleration by matrix density. We demonstrate the benefit of our approach for generalized matrix multiplication operations over large matrices with up to four billion elements. To connect the effectiveness of our approach with machine learning applications, we performed Gramian matrix computation via generalized matrix multiplications. Our experiments show that our approach achieves more than 2x performance speed-up, and up to 96.1% computation improvement, compared to a state of the art Spark MLlib for dense matrices.

  8. Scaling up physical activity interventions worldwide: stepping up to larger and smarter approaches to get people moving.

    Science.gov (United States)

    Reis, Rodrigo S; Salvo, Deborah; Ogilvie, David; Lambert, Estelle V; Goenka, Shifalika; Brownson, Ross C

    2016-09-24

    The global pandemic of physical inactivity requires a multisectoral, multidisciplinary public-health response. Scaling up interventions that are capable of increasing levels of physical activity in populations across the varying cultural, geographic, social, and economic contexts worldwide is challenging, but feasible. In this paper, we review the factors that could help to achieve this. We use a mixed-methods approach to comprehensively examine these factors, drawing on the best available evidence from both evidence-to-practice and practice-to-evidence methods. Policies to support active living across society are needed, particularly outside the health-care sector, as demonstrated by some of the successful examples of scale up identified in this paper. Researchers, research funders, and practitioners and policymakers in culture, education, health, leisure, planning, and transport, and civil society as a whole, all have a role. We should embrace the challenge of taking action to a higher level, aligning physical activity and health objectives with broader social, environmental, and sustainable development goals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Antiretroviral Treatment Scale-Up and Tuberculosis Mortality in High TB/HIV Burden Countries: An Econometric Analysis.

    Science.gov (United States)

    Yan, Isabel; Bendavid, Eran; Korenromp, Eline L

    2016-01-01

    Antiretroviral therapy (ART) reduces mortality in patients with active tuberculosis (TB), but the population-level relationship between ART coverage and TB mortality is untested. We estimated the reduction in population-level TB mortality that can be attributed to increasing ART coverage across 41 high HIV-TB burden countries. We compiled TB mortality trends between 1996 and 2011 from two sources: (1) national program-reported TB death notifications, adjusted for annual TB case detection rates, and (2) WHO TB mortality estimates. National coverage with ART, as proportion of HIV-infected people in need, was obtained from UNAIDS. We applied panel linear regressions controlling for HIV prevalence (5-year lagged), coverage of TB interventions (estimated by WHO and UNAIDS), gross domestic product per capita, health spending from domestic sources, urbanization, and country fixed effects. Models suggest that that increasing ART coverage was followed by reduced TB mortality, across multiple specifications. For death notifications at 2 to 5 years following a given ART scale-up, a 1% increase in ART coverage predicted 0.95% faster mortality rate decline (p = 0.002); resulting in 27% fewer TB deaths in 2011 alone than would have occurred without ART. Based on WHO death estimates, a 1% increase in ART predicted a 1.0% reduced TB death rate (peconometric analysis supports a substantial impact of ART on population-level TB mortality realized already within the first decade of ART scale-up, that is apparent despite variable-quality mortality data.

  10. Isolation of a novel high erythritol-producing Pseudozyma tsukubaensis and scale-up of erythritol fermentation to industrial level.

    Science.gov (United States)

    Jeya, Marimuthu; Lee, Kyoung-Mi; Tiwari, Manish Kumar; Kim, Jung-Soo; Gunasekaran, Paramasamy; Kim, Sang-Yong; Kim, In-Won; Lee, Jung-Kul

    2009-05-01

    This study isolated a novel erythritol-producing yeast strain, which is capable of growth at high osmolarity. Characteristics of the strain include asexual reproduction by multilateral budding, absence of extracellular starch-like compounds, and a negative Diazonium blue B color reaction. Phylogenetic analysis based on the 26S rDNA sequence and physiological analysis indicated that the strain belongs to the species Pseudozyma tsukubaensis and has been named P. tsukubaensis KN75. When P. tsukubaensis KN75 was cultured aerobically in a fed-batch culture with glucose as a carbon source, it produced 245 g/L of erythritol, corresponding to 2.86 g/L/h productivity and 61% yield, the highest erythritol yield ever reported by an erythritol-producing microorganism. Erythritol production was scaled up from a laboratory scale (7 L fermenter) to pilot (300 L) and plant (50,000 L) scales using the dissolved oxygen as a scale-up parameter. Erythritol production at the pilot and plant scales was similar to that at the laboratory scale, indicating that the production of erythritol by P. tsukubaensis KN75 holds commercial potential.

  11. Climate-related environmental stress in intertidal grazers: scaling-up biochemical responses to assemblage-level processes

    Directory of Open Access Journals (Sweden)

    Elena Maggi

    2016-10-01

    Full Text Available Background Organisms are facing increasing levels of environmental stress under climate change that may severely affect the functioning of biological systems at different levels of organization. Growing evidence suggests that reduction in body size is a universal response of organisms to global warming. However, a clear understanding of whether extreme climate events will impose selection directly on phenotypic plastic responses and how these responses affect ecological interactions has remained elusive. Methods We experimentally investigated the effects of extreme desiccation events on antioxidant defense mechanisms of a rocky intertidal gastropod (Patella ulyssiponensis, and evaluated how these effects scaled-up at the population and assemblage levels. Results With increasing levels of desiccation stress, limpets showed significant lower levels of total glutathione, tended to grow less and had reduced per capita interaction strength on their resources. Discussion Results suggested that phenotypic plasticity (i.e., reduction in adults’ body size allowed buffering biochemical responses to stress to scale-up at the assemblage level. Unveiling the linkages among different levels of biological organization is key to develop indicators that can anticipate large-scale ecological impacts of climate change.

  12. Scaling up health interventions in resource-poor countries: what role does research in stated-preference framework play?

    Directory of Open Access Journals (Sweden)

    Pokhrel Subhash

    2006-03-01

    Full Text Available Abstract Despite improved supply of health care services in low-income countries in the recent past, their uptake continues to be lower than anticipated. This has made it difficult to scale-up those interventions which are not only cost-effective from supply perspectives but that might have substantial impacts on improving the health status of these countries. Understanding demand-side barriers is therefore critically important. With the help of a case study from Nepal, this commentary argues that more research on demand-side barriers needs to be carried out and that the stated-preference (SP approach to such research might be helpful. Since SP techniques place service users' preferences at the centre of the analysis, and because preferences reflect individual or social welfare, SP techniques are likely to be helpful in devising policies to increase social welfare (e.g. improve