486 research outputs found
How Does an Enriched Environment Impact Hippocampus Brain Plasticity?
Brain plasticity is profoundly impacted by oneâs living environment. The hippocampus, involved in learning and memory, is highly susceptible to plasticity. Raising rodents in an âenriched environmentâ (EE) increases learning and memorization aptitudes and decreases the anxiety of the animals. EE consists of a combination of running wheels for voluntary physical exercise, complex inanimate toys, nests, mazes, etc. all of which favor sensory stimulations and social enrichment. EE housing concomitantly increases proliferation and survival of neurons and glia in the dentate gyrus of the hippocampus, induces changes in neuronal morphology, modifies synaptic plasticity, and favors angiogenesis. The mechanisms underlying the effects of EE on plasticity, which have recently been investigated are reviewed here, including the role of glia, the involvement of molecular factors including neurotransmitters (glutamate), neurotrophic factors (BDNF), adipokines (leptin and adiponectin), chemokines, cytokines, and hormones (corticosteroid and thyroid hormones), and at a higher level, the various systems involved (neural networks and hormonal systems). We emphasize recent findings that demonstrate the major role of the immune system in modulating EE-induced changes to hippocampal plasticity. This process involves a variety of immune cells (including macrophages, microglia, natural killer, B-cells, and T-cells), although the mechanisms are yet to be fully elucidated
Designing a paediatric study for an antimalarial drug including prior information from adults
International audienceThe objectives of this study were to design a pharmacokinetic (PK) study by using information about adults and evaluate the robustness of the recommended design through a case study of mefloquine. PK data about adults and children were available from two different randomized studies of the treatment of malaria with the same artesunate-mefloquine combination regimen. A recommended design for pediatric studies of mefloquine was optimized on the basis of an extrapolated model built from adult data through the following approach. (i) An adult PK model was built, and parameters were estimated by using the stochastic approximation expectation-maximization algorithm. (ii) Pediatric PK parameters were then obtained by adding allometry and maturation to the adult model. (iii) A D-optimal design for children was obtained with PFIM by assuming the extrapolated design. Finally, the robustness of the recommended design was evaluated in terms of the relative bias and relative standard errors (RSE) of the parameters in a simulation study with four different models and was compared to the empirical design used for the pediatric study. Combining PK modeling, extrapolation, and design optimization led to a design for children with five sampling times. PK parameters were well estimated by this design with few RSE. Although the extrapolated model did not predict the observed mefloquine concentrations in children very accurately, it allowed precise and unbiased estimates across various model assumptions, contrary to the empirical design. Using information from adult studies combined with allometry and maturation can help provide robust designs for pediatric studies
Urban Revitalization through Art, Community, and Ecology: The Heidelberg Project
Once known as the Motor City, Detroit is now rusted over with 90,000 vacant parcels and a 22%
unemployment rate. Decline of manufacturing jobs, combined with a complex history of racism and
discrimination, led to unprecedented population collapse and abandonment. The 2010 census revealed
the dramatic exodus from Detroit was even greater than predicted: just over 713,000 residents remain,
down from nearly 2 million in 1950. Leftover stretches of vacant land, totaling more than 40 square
miles, pose an enormous physical and psychological challenge to residents and city officials forced to
manage with what remains. Despite the challenges of vacant land, disenfranchisement, and economic
hardship, many still see beauty in whatâs left of the city. Twenty-five years ago, Detroit-native Tyree
Guyton created the Heidelberg Project, a two-block long environmental artscape on the cityâs eastside.
The artwork became a beacon for his neighborhood and others like it, defiantly resisting the destruction
wrought by neglect and disinvestment.
The research and design presented in this document expands the scope of the Heidelberg Project into
a long-term vision for neighborhood redevelopment called the Heidelberg Cultural Village. This project
lays the groundwork for the Cultural Village, a model for art-based neighborhood redevelopment in
Detroit and other post-industrial cities. The work is presented in four chapters: Christian Runge examines
how the Heidelberg Cultural Village can be integrated with emerging ecological and cultural land uses
specific to a post urban Detroit. Fai Foenâs work focuses on an alternative economic model that invests
in the local economy and builds on existing human capacity to support sustainable redevelopment in
Rustbelt communities. Sarah Alward explores how an art-based urban farm can allow for a diverse range
of contributions from community members, creating an inclusive space to grow fresh, healthy food that
has the potential to increase neighborhood investment and involvement. Finally, Dana Petit illustrates
how a healing garden can respond to the social, psychological, and physical health issues stemming from
the McDougall-Hunt neighborhoodâs experience with abandonment and poverty. Together, these design
interventions are intended to serve as an incubator for physical, economic, and cultural sustainability and
the center of community life for the McDougall-Hunt neighborhood.Master of Landscape ArchitectureNatural Resources and EnvironmentUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/84207/1/Heidelberg Opus 2011.pd
Effect of subclinical and overt form of rat maternal hypothyroidism on offspring endochondral bone formation
Maternal hypothyroidism in its overt form affects skeletal development of the offspring, but these data are not available for the subclinical form which is becoming very frequent among pregnant women. We hypothesized that the subclinical form of hypothyroidism in rat dams, influences the process of offspring endochondral ossification affecting proliferation and differentiation of chondrocytes, osteoclasts and osteoblasts in pups. Seven-day-old male pups (n=18) derived from control dams and dams treated with a low dose (1.5 mg/L) or high dose (150 mg/L) of propylthiouracil in drinking water during pregnancy and lactation were used. Histomorphometric analysis of pups tibia proximal growth plate, expression of mRNA, immunohistochemical and histochemical visualization of extracellular matrix components was performed. The length of the tibia was reduced in hypothyroid pups. Secretion of type 2 and 10 collagens in the subclinical and overt form were lower while the amount of glycosaminoglycans was higher when compared with controls. Down-regulated tartrate resistant acid phosphatase mRNA indicated altered osteoclasts function while lower expression of dentin matrix acid protein-1 mRNA and reduced synthesis of type 1 collagen accentuated a compromised bone formation in the overt form of hypothyroidism. The subclinical form of maternal hypothyroidism had a negative effect on the differentiation of hypertrophic chondrocytes and calcified cartilage removal in 7-day-old pups. In addition, overt hypothyroidism had a negative effect on the proliferation of chondrocytes and deposition of osteoid. Both forms of hypothyroidism resulted in a decrease of tibia length due to changes in growth plate formation
OSSOS. IX. Two Objects in Neptune's 9: 1 Resonance - Implications for Resonance Sticking in the Scattering Population
We discuss the detection in the Outer Solar System Origins Survey (OSSOS) of
two objects in Neptune's distant 9:1 mean motion resonance at semimajor axis
~au. Both objects are securely resonant on 10~Myr timescales,
with one securely in the 9:1 resonance's leading asymmetric libration island
and the other in either the symmetric or trailing asymmetric island. These
objects are the largest semimajor axis objects with secure resonant
classifications, and their detection in a carefully characterized survey allows
for the first robust resonance population estimate beyond 100~au. The detection
of these objects implies a 9:1 resonance population of objects
with (~km) on similar orbits (95\% confidence range
of ). Integrations over 4~Gyr of an ensemble of clones
spanning these objects' orbit fit uncertainties reveal that they both have
median resonance occupation timescales of ~Gyr. These timescales are
consistent with the hypothesis that these objects originate in the scattering
population but became transiently stuck to Neptune's 9:1 resonance within the
last ~Gyr of solar system evolution. Based on simulations of a model of
the current scattering population, we estimate the expected resonance sticking
population in the 9:1 resonance to be 1000-4500 objects with ; this
is marginally consistent with the OSSOS 9:1 population estimate. We conclude
that resonance sticking is a plausible explanation for the observed 9:1
population, but we also discuss the possibility of a primordial 9:1 population,
which would have interesting implications for the Kuiper belt's dynamical
history.Comment: accepted for publication in A
The PedAL/EuPAL Project:A Global Initiative to Address the Unmet Medical Needs of Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia
The prognosis of children with acute myeloid leukemia (AML) has improved incrementally over the last few decades. However, at relapse, overall survival (OS) is approximately 40â50% and is even lower for patients with chemo-refractory disease. Effective and less toxic therapies are urgently needed for these children. The Pediatric Acute Leukemia (PedAL) program is a strategic global initiative that aims to overcome the obstacles in treating children with relapsed/refractory acute leukemia and is supported by the Leukemia and Lymphoma Society in collaboration with the Childrenâs Oncology Group, the Innovative Therapies for Children with Cancer consortium, and the European Pediatric Acute Leukemia (EuPAL) foundation, amongst others. In Europe, the study is set up as a complex clinical trial with a stratification approach to allocate patients to sub-trials of targeted inhibitors at relapse and employing harmonized response and safety definitions across sub-trials. The PedAL/EuPAL international collaboration aims to determine new standards of care for AML in a first and second relapse, using biology-based selection markers for treatment stratification, and deliver essential data to move drugs to front-line pediatric AML studies. An overview of potential treatment targets in pediatric AML, focused on drugs that are planned to be included in the PedAL/EuPAL project, is provided in this manuscript.</p
The PedAL/EuPAL Project:A Global Initiative to Address the Unmet Medical Needs of Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia
The prognosis of children with acute myeloid leukemia (AML) has improved incrementally over the last few decades. However, at relapse, overall survival (OS) is approximately 40â50% and is even lower for patients with chemo-refractory disease. Effective and less toxic therapies are urgently needed for these children. The Pediatric Acute Leukemia (PedAL) program is a strategic global initiative that aims to overcome the obstacles in treating children with relapsed/refractory acute leukemia and is supported by the Leukemia and Lymphoma Society in collaboration with the Childrenâs Oncology Group, the Innovative Therapies for Children with Cancer consortium, and the European Pediatric Acute Leukemia (EuPAL) foundation, amongst others. In Europe, the study is set up as a complex clinical trial with a stratification approach to allocate patients to sub-trials of targeted inhibitors at relapse and employing harmonized response and safety definitions across sub-trials. The PedAL/EuPAL international collaboration aims to determine new standards of care for AML in a first and second relapse, using biology-based selection markers for treatment stratification, and deliver essential data to move drugs to front-line pediatric AML studies. An overview of potential treatment targets in pediatric AML, focused on drugs that are planned to be included in the PedAL/EuPAL project, is provided in this manuscript.</p
PHA4GE quality control contextual data tags:standardized annotations for sharing public health sequence datasets with known quality issues to facilitate testing and training
As public health laboratories expand their genomic sequencing and bioinformatics capacity for the surveillance of different pathogens, labs must carry out robust validation, training, and optimization of wet- and dry-lab procedures. Achieving these goals for algorithms, pipelines and instruments often requires that lower quality datasets be made available for analysis and comparison alongside those of higher quality. This range of data quality in reference sets can complicate the sharing of sub-optimal datasets that are vital for the community and for the reproducibility of assays. Sharing of useful, but sub-optimal datasets requires careful annotation and documentation of known issues to enable appropriate interpretation, avoid being mistaken for better quality information, and for these data (and their derivatives) to be easily identifiable in repositories. Unfortunately, there are currently no standardized attributes or mechanisms for tagging poor-quality datasets, or datasets generated for a specific purpose, to maximize their utility, searchability, accessibility and reuse. The Public Health Alliance for Genomic Epidemiology (PHA4GE) is an international community of scientists from public health, industry and academia focused on improving the reproducibility, interoperability, portability, and openness of public health bioinformatic software, skills, tools and data. To address the challenges of sharing lower quality datasets, PHA4GE has developed a set of standardized contextual data tags, namely fields and terms, that can be included in public repository submissions as a means of flagging pathogen sequence data with known quality issues, increasing their discoverability. The contextual data tags were developed through consultations with the community including input from the International Nucleotide Sequence Data Collaboration (INSDC), and have been standardized using ontologies - community-based resources for defining the tag properties and the relationships between them. The standardized tags are agnostic to the organism and the sequencing technique used and thus can be applied to data generated from any pathogen using an array of sequencing techniques. The tags can also be applied to synthetic (lab created) data. The list of standardized tags is maintained by PHA4GE and can be found at https://github.com/pha4ge/contextual_data_QC_tags. Definitions, ontology IDs, examples of use, as well as a JSON representation, are provided. The PHA4GE QC tags were tested, and are now implemented, by the FDA's GenomeTrakr laboratory network as part of its routine submission process for SARS-CoV-2 wastewater surveillance. We hope that these simple, standardized tags will help improve communication regarding quality control in public repositories, in addition to making datasets of variable quality more easily identifiable. Suggestions for additional tags can be submitted to PHA4GE via the New Term Request Form in the GitHub repository. By providing a mechanism for feedback and suggestions, we also expect that the tags will evolve with the needs of the community.</p
Evaluation study of the suitability of instrumentation to measure ambient NH3 concentrations under field conditions
The uncertainties in emissions of ammonia (NH3) in Europe are large, partially due to the difficulty in monitoring
of ambient concentrations due to its sticky nature. In the European Monitoring and Evaluation Program (EMEP)
the current recommended guidelines to measure NH3 are by coated annular denuders with offline analysis. This
method, however, is no longer used in most European countries and each one has taken a different strategy to
monitor atmospheric ammonia due to the increase of commercial NH3 monitoring instrumentation available over
the last 20 years. In June 2014, a 3 year project funded under the European Metrology Research Programme,
âMetrology for Ammonia in Ambient Airâ (MetNH3), started with the aim to develop metrological traceability
for the measurement of NH3 in air from primary gas mixtures and instrumental standards to field application.
This study presents the results from the field intercomparison (15 instruments) which was held in South East Scotland in August 2016 over an intensively managed grassland. The study compared active sampling methods
to a meteorological traceable method which was developed during the project with the aim to produce a series
of guidelines for ambient NH3 measurements. Preliminary results highlight both the importance of inlets and
management of relative humidity in the measurement of ambient NH3 and of the requirement to carry out frequent
intercomparison of NH3 instrumentation. Overall, it would be recommended from this study that a WMO-GAW
world centre for NH3 would be established and support integration of standards into both routine and research
measurements
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