Computational Investigation of the Changing Patterns of Subtype Specific NMDA Receptor Activation during Physiological Glutamatergic Neurotransmission

NMDA receptors (NMDARs) are the major mediator of the postsynaptic response during synaptic neurotransmission. The diversity of roles for NMDARs in influencing synaptic plasticity and neuronal survival is often linked to selective activation of multiple NMDAR subtypes (NR1/NR2A-NMDARs, NR1/NR2B-NMDARs, and triheteromeric NR1/NR2A/NR2B-NMDARs). However, the lack of available pharmacological tools to block specific NMDAR populations leads to debates on the potential role for each NMDAR subtype in physiological signaling, including different models of synaptic plasticity. Here, we developed a computational model of glutamatergic signaling at a prototypical dendritic spine to examine the patterns of NMDAR subtype activation at temporal and spatial resolutions that are difficult to obtain experimentally. We demonstrate that NMDAR subtypes have different dynamic ranges of activation, with NR1/NR2A-NMDAR activation sensitive at univesicular glutamate release conditions, and NR2B containing NMDARs contributing at conditions of multivesicular release. We further show that NR1/NR2A-NMDAR signaling dominates in conditions simulating long-term depression (LTD), while the contribution of NR2B containing NMDAR significantly increases for stimulation frequencies that approximate long-term potentiation (LTP). Finally, we show that NR1/NR2A-NMDAR content significantly enhances response magnitude and fidelity at single synapses during chemical LTP and spike timed dependent plasticity induction, pointing out an important developmental switch in synaptic maturation. Together, our model suggests that NMDAR subtypes are differentially activated during different types of physiological glutamatergic signaling, enhancing the ability for individual spines to produce unique responses to these different inputs

Liquid Methane/Liquid Oxygen Propellant Conditioning Feed System (PCFS) Test Rigs

As part of their Propulsion and Cryogenic Advanced Development (PCAD) program, NASA has embarked upon an effort to develop chemical rocket engines which utilize non-toxic, cryogenic propellants such as liquid oxygen (LO2) and liquid methane (LCH4). This effort includes the development and testing of a 100 lbf Reaction Control Engine (RCE) that will be used to evaluate the performance of a LO2/LCH4 rocket engine over a broad range of propellant temperatures and pressures. This testing will take place at NASA-Glenn Research Center's (GRC) Research Combustion Laboratory (RCL) test facility in Cleveland, OH, and is currently scheduled to begin in late 2008. While the initial tests will be performed at sea level, follow-on testing will be performed at NASA-GRC's Altitude Combustion Stand (ACS) for altitude testing. In support of these tests, Sierra Lobo, Inc. (SLI) has designed, developed, and fabricated two separate portable propellant feed systems under the Propellant Conditioning and Feed System (PCFS) task: one system for LCH4, and one for LO2. These systems will be capable of supplying propellants over a large range of conditions from highly densified to several hundred pounds per square inch (psi) saturated. This paper presents the details of the PCFS design and explores the full capability of these propellant feed systems

Impact of hospital diagnosis-specific quality measures on patients’ experience of hospital care: Evidence from 14 states, 2009-2011

In order to assess consistency across quality measures for Untied States hospitals, this paper uses patient responses to the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey for three years (2009-2011) from 1,333 acute-care hospitals in fourteen states to analyze patterns in hospital-reported patient experience-of-care scores by diagnosis-specific process and outcome measures for acute myocardial infarction, heart failure, and pneumonia. We also evaluate how scores have changed over the three-year period. We find significant differences in patient experience-of-care scores for 195 out of 230 relationships between HCAHPS patient experience-of-care scores and 23 diagnosis-specific process and outcomes measures. We find nearly no significant differences in changes in scores from 2009-2011 (8 out of 230) when comparing the same experience-of-care and diagnosis-specific quality measures. For the majority of measures, high scores on the quality metrics were associated with high patient experience-of-care scores

Trans World Radio - Culvert Design

Trans World Radio (TWR) is a mission organization focused on broadcasting the Gospel around the world. TWR now serves 190 countries by transmitting in 275 languages, using radio to deliver the message to as many people as possible. The organization’s West Africa Transmitter Site in Benin currently has accessibility problems due to high streamflows and saturated ground conditions during the rainy season. The site also needs a secure perimeter to reduce trespassing and theft. To address these issues, our client, Garth Kennedy, Director of the West Africa Transmitter Station, has asked the team to design two culverts, one at the upstream property boundary and one at the downstream boundary. Culverts are advantageous for this scenario because they can act as a bridge, while the pipe size can be restricted to inhibit trespassing. Once the culverts are built, the fence and perimeter road can be extended over them. For both sides of the property, the team has designed a series of U-shaped, pre-cast concrete box culverts. The team calculated the design flows based on rainfall data and the topography of the site to determine the size and number of box sections. The team has also designed the culverts and the supporting concrete structures to bear the load of vehicles and the machinery on site. TWR plans to construct the pre-cast culverts on-site, and then build the supporting structures and install the culverts during their dry season.https://mosaic.messiah.edu/engr2021/1017/thumbnail.jp

Stormwater Management for Greenwood Hills Bible Camp

The stormwater team addresses flooding and erosion issues. In the spring of 2022, the team analyzed erosion problems for Greenwood Hills Bible Camp near Chambersburg PA and designed a system to capture and divert the runoff that is causing erosion. The design includes collection of the runoff with French drains and rock channels and conveyance of the water through a culvert with discharge down-gradient of affected houses. The system should lessen the erosion affecting the camp road and fix nuisance flooding and erosion at the residences. In the fall of 2021, the team partnered with the City of Harrisburg and Capital Region Water to address flooding in the Allison Hill neighborhood of Harrisburg Pennsylvania and designed a plan to mitigate this problem for neighborhood residents. Funding for this work provided by The Collaboratory for Strategic Partnerships and Applied Research.https://mosaic.messiah.edu/engr2022/1018/thumbnail.jp

Influence of Inflammatory and Oxidative Stress Pathways on Longitudinal Symptom Experiences in Children With Leukemia

Purpose: The purpose of this study was to explore the influence of oxidative stress (F2-isoprostanes) and inflammatory (interleukin [IL]-8) biomarkers on symptom trajectories during the first 18 months of childhood leukemia treatment. Method: A repeated-measures design was used to evaluate symptoms experienced by 218 children during treatment. A symptom cluster (fatigue, pain, and nausea) was explored over four time periods: initiation of post-induction therapy, 4 and 8 months into post-induction therapy, and the beginning of maintenance therapy (12 months postinduction). F2-isoprostanes and IL-8 were evaluated in cerebrospinal fluid (CSF) samples collected at baseline (diagnosis) and then at the four time periods. The longitudinal relationships of these biomarkers with the symptom cluster were examined using the longitudinal parallel process. Results: Pain and fatigue levels were highest during the post-induction phases of treatment and decreased slightly during maintenance therapy, while nausea scores were relatively stable. Even in the later phases of treatment, children continued to experience symptoms. CSF levels of the biomarkers increased during the post-induction phases of treatment. Early increases in the biomarkers were associated with more severe symptoms during the same period; patients who had increased biomarkers over time also experienced more severe symptoms over time. Conclusions: Findings reveal that children experienced symptoms throughout the course of leukemia treatment and support hypothesized longitudinal relationships of oxidative stress and inflammatory biomarkers with symptom severity. Activation of the biomarker pathways during treatment may explain underlying mechanisms of symptom experiences and identify which children are at risk for severe symptoms.National Institutes of Health [R01CA1693398]This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Impact of hospital characteristics on patients’ experience of hospital care: Evidence from 14 states, 2009-2011

This paper uses patient responses to the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey for three years (2009-2011) from 1,333 acute-care hospitals in fourteen states to analyze patterns in 10 hospital-reported patient experience-of-care scores by 29 characteristics classified as: patient characteristics, payer source, patient severity, hospital characteristics, hospital operations, and market characteristics. We also evaluate how scores have changed over the three-year period. We find significant differences in patient experience-of-care scores by hospital characteristics for 250 out of 290 HCAHPS-hospital characteristic combinations measured. We find fewer significant differences in changes in scores from 2009-2011 (135 out of 290), with hospitals categorized as high scoring also reporting consistently greater improvement. We conclude that patient experience-of-care scores vary by hospital characteristics, although improvements in scores show less variety by hospital categorization

Clinical factors associated with fatigue over time in paediatric oncology patients receiving chemotherapy

The purpose of this study was to investigate the relationships between clinical factors (including haemoglobin value, chemotherapeutic agents, and corticosteroid use) and changing patterns of fatigue before and for the next 10 days following the start of a new round of chemotherapy in children with cancer. A prospective longitudinal design was used to collect data from 48 paediatric oncology patients who were about to begin a new round of chemotherapy and their parents. Fatigue levels were assessed using multidomain questionnaires with three categories of patient self-report (including ‘General Fatigue', ‘Sleep/Rest Fatigue', and ‘Cognitive Fatigue') and four categories of parent proxy-report (including ‘Lack of Energy', ‘Unable to Function', ‘Altered Sleep', and ‘Altered Mood'). The findings suggest that fatigue from both patient self-report and parent proxy-report changed significantly over time. The major findings from this study are that patients have more problems with fatigue in the first few days after the start of a cycle of chemotherapy. Corticosteroid use and haemoglobin value were associated with significant increases in fatigue that were sustained for several days and reached the highest level of fatigue at day 5 for those receiving concurrent steroids. The association of chemotherapeutic agents with fatigue varied between patient self-report and parent report, but the type of chemotherapeutic agents used was not associated with most changes in fatigue

Lived Experience of Caregivers of Family-Centered Care in the Neonatal Intensive Care Unit: “Evocation of Being at Home

Background: In recent decades, family-centered care (FCC) has come to be known, accepted, and reported as the best care strategy for admitted children and their families. However, in spite of the increasing application of this approach, the experiences of the caregivers have not yet been studied. Objectives: The present study aimed at the description and interpretation of the FCC experience in two neonatal intensive care units (NICU) at Shiraz University of Medical Sciences. Methods: This study was conducted through the hermeneutic phenomenological approach. Semi-structured interviews were conducted with 17 professional and familial caregivers, and their interactions were observed in three work shifts. The interviews were audiotaped and transcribed verbatim. After observations, field notes were also written. Finally, the data were analyzed through van Manen’s methodology. Results: One of the essential themes that emerged in this study was the “evocation of being at home” among familial and even professional caregivers. This theme had three subthemes: i.e., “meta-family interaction,” “comprehensive support,” and “reconstruction of a normal family.” Accordingly, FCC eliminated borders between professional and non-professional caregivers and built close relationships among them in the NICU. It also provided for the needs of neonates, their families, and even professional caregivers through perceived and received support. Conclusions: Parents of the neonates admitted to the NICU experience hard moments. They not only play the role of primary caregivers, but they also receive the care. Focusing on the different meanings of this care from the caregivers’ points of view and having managers provide certain requirements can guarantee the establishment of comprehensive care for clients and proper support for the staff in this uni