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OBJECTIVES/SPECIFIC AIMS: The central goal of this proposal is to characterize the mechanisms that mediate success or failure of immature intestinal barrier in necrotizing enterocilitis. METHODS/STUDY POPULATION: To do this, I will utilize stem cell derived human intestinal organoids (HIOs), an innovative model of the immature intestine, and a cohort of bacterial isolates collected from premature infants who developed NEC to interrogate the cause-effect relationship of these strains on maintenance of the intestinal barrier. I hypothesize that the epithelial response to bacterial colonization is strain-dependent and results in differences in inflammatory signaling that shape epithelial barrier function in the immature intestine. RESULTS/ANTICIPATED RESULTS: Preliminary data shows that colonization of HIOs with different bacteria leads to species-specific changes in barrier function, and some species selectively damage the epithelial barrier while others enhance epithelial barrier function. I have identified key inflammatory signals that serve as central drivers of intestinal barrier function. DISCUSSION/SIGNIFICANCE OF IMPACT: Characterization of this process is expected to substantially advance scientific understanding of early events in NEC pathogenesis and lead to new opportunities for targeted therapeutic intervention to accelerate barrier maturation or prevent hyperinflammatory reactivity in the neonatal intestine. The research proposed in this application represents an entirely novel approach to studying host-microbial interactions in the immature. Conceptually, this novel translational approach will help to define the pivotal role of colonizing bacteria in initiating epithelial inflammation in NEC patients.
A complete text-to-speech system has been created by the authors, based on a tube resonance model of the vocal tract and a development of Carré’s “Distinctive Region Model”, which is in turn based on the formant-sensitivity findings of Fant and Pauli (1974), to control the tube. In order to achieve this goal, significant long-term linguistic research has been involved, including rhythm and intonation studies, as well as the development of low-level articulatory data and rules to drive the model, together with the necessary tools, parsers, dictionaries and so on. The tools and the current system are available under a General Public License, and are described here, with further references in the paper, including samples of the speech produced, and figures illustrating the system description.
We summarize the use of radiocarbon produced by spallation in meteorites in space to determine their terrestrial age or residence time. This “age” gives us important information as it can be compared to the rates of weathering and infall of meteorites. The processes that affect the collection of meteorites in a given area can be related to the rates of infall of new meteorites, and the rate of removal by chemical weathering and physical erosion.
To determine if total lifetime physical activity (PA) is associated with better cognitive functioning with aging and if cerebrovascular function mediates this association. A sample of 226 (52.2% female) community dwelling middle-aged and older adults (66.5±6.4 years) in the Brain in Motion Study, completed the Lifetime Total Physical Activity Questionnaire and underwent neuropsychological and cerebrovascular blood flow testing. Multiple robust linear regressions were used to model the associations between lifetime PA and global cognition after adjusting for age, sex, North American Adult Reading Test results (i.e., an estimate of premorbid intellectual ability), maximal aerobic capacity, body mass index and interactions between age, sex, and lifetime PA. Mediation analysis assessed the effect of cerebrovascular measures on the association between lifetime PA and global cognition. Post hoc analyses assessed past year PA and current fitness levels relation to global cognition and cerebrovascular measures. Better global cognitive performance was associated with higher lifetime PA (p=.045), recreational PA (p=.021), and vigorous intensity PA (p=.004), PA between the ages of 0 and 20 years (p=.036), and between the ages of 21 and 35 years (p<.0001). Cerebrovascular measures did not mediate the association between PA and global cognition scores (p>.5), but partially mediated the relation between current fitness and global cognition. This study revealed significant associations between higher levels of PA (i.e., total lifetime, recreational, vigorous PA, and past year) and better cognitive function in later life. Current fitness levels relation to cognitive function may be partially mediated through current cerebrovascular function. (JINS, 2015, 21, 816–830)
IAU Commission 29 - Stellar Spectra has been one of the IAU commissions from the onset, until its dissolution at the most recent IAU General Assembly in Honolulu in 2015. This commission belonged to IAU Division G (“Stars and Stellar Physics”), the latter committed with fostering research in stellar astrophysics. Within the general field of stellar astrophysics, stellar spectroscopy plays a key role, as stellar spectra are a powerful tool providing a view into the detailed physical properties of stars and the physical processes occuring within them.
This article is an executive summary of a report from the Centers for Disease Control and Prevention Ventilator-Associated Pneumonia Surveillance Definition Working Group, entitled “Developing a new, national approach to surveillance for ventilator-associated events” and published in Critical Care Medicine. The full report provides a comprehensive description of the Working Group process and outcome.
In September 2011, the Centers for Disease Control and Prevention (CDC) convened a Ventilator-Associated Pneumonia (VAP) Surveillance Definition Working Group to organize a formal process for leaders and experts of key stakeholder organizations to discuss the challenges of VAP surveillance definitions and to propose new approaches to VAP surveillance in adult patients (Table 1).
Relatively little is known of the use of systematic review and synthesis
methods of non-randomised psychiatric epidemiological studies, which play
a vital role in aetiological research, planning and policy-making.
To evaluate reviews of psychiatric epidemiological studies of functional
mental disorders that employed synthesis methods such as systematic
review or meta-analysis, or other forms of quantitative review.
We searched the literature to identify appropriate reviews published
during the period 1996 to April 2009. Selected reviews were evaluated
using published review guidelines.
We found 106 reviews in total, of which 38 (36%) did not mention method
of data abstraction from primary studies at all. Many failed to mention
study quality, publication bias, bias and confounding. In 73 studies that
performed a meta-analysis, 58 (79%) tested for heterogeneity and of
these, 47 found significant heterogeneity. Studies that detected
heterogeneity made some allowance for this. A major obstacle facing
reviewers is the wide variation between primary studies in the use of
instruments to measure outcomes and in sampling methods used.
Many deficiencies found in systematic reviews are potentially remediable,
although synthesis of primary study findings in a field characterised by
so many sources of heterogeneity will remain challenging.
The purpose of this article is to set the context for this special issue of Disaster Medicine and Public Health Preparedness on the allocation of scarce resources in an improvised nuclear device incident. A nuclear detonation occurs when a sufficient amount of fissile material is brought suddenly together to reach critical mass and cause an explosion. Although the chance of a nuclear detonation is thought to be small, the consequences are potentially catastrophic, so planning for an effective medical response is necessary, albeit complex. A substantial nuclear detonation will result in physical effects and a great number of casualties that will require an organized medical response to save lives. With this type of incident, the demand for resources to treat casualties will far exceed what is available. To meet the goal of providing medical care (including symptomatic/palliative care) with fairness as the underlying ethical principle, planning for allocation of scarce resources among all involved sectors needs to be integrated and practiced. With thoughtful and realistic planning, the medical response in the chaotic environment may be made more effective and efficient for both victims and medical responders.
(Disaster Med Public Health Preparedness. 2011;5:S20-S31)
For efficient and effective medical responses to mass casualty events, detailed advanced planning is required. For federal responders, this is an ongoing responsibility. The US Department of Health and Human Services (DHHS) prepares playbooks with formal, written plans that are reviewed, updated, and exercised regularly. Recognizing that state and local responders with fewer resources may be helped in creating their own event-specific response plans, subject matter experts from the range of sectors comprising the Scarce Resources for a Nuclear Detonation Project, provided for this first time a state and local planner's playbook template for responding to a nuclear detonation. The playbook elements are adapted from DHHS playbooks with appropriate modification for state and local planners. Individualization by venue is expected, reflecting specific assets, populations, geography, preferences, and expertise. This playbook template is designed to be a practical tool with sufficient background information and options for step-by-step individualized planning and response.
(Disaster Med Public Health Preparedness. 2011;5:S89-S97)
The hallmark of a successful response to a nuclear detonation will be the resilience of the community, region, and nation. An incident of this magnitude will rapidly become a national incident; however, the initial critical steps to reduce lives lost, save the lives that can be saved with the resources available, and understand and apply resources available to a complex and dynamic situation will be the responsibility of the local and regional responders and planners. Expectations of the public health and health care systems will be met to the extent possible by coordination, cooperation, and an effort to produce as consistent a response as possible for the victims. Responders will face extraordinarily stressful situations, and their own physical and psychological health is of great importance to optimizing the response. This article illustrates through vignettes and supporting text how the incident may unfold for the various components of the health and medical systems and provides additional context for the discipline-related actions outlined in the state and local planners’ playbook.
(Disaster Med Public Health Preparedness. 2011;5:S73-S88)
Experimental measurements of material effects induced by the passage of sharp shock fronts require techniques which provide high temporal resolution and high spatial resolution. Since typical shock velocities are a few microns per nanosecond, sub-nanosecond probing requires sub-micron spatial resolution. In our experiments, the required temporal resolution is furnished using picosecond laser generated shock waves and picosecond spectroscopy. The spatial resolution is furnished by engineering nanometer scale structures into our shock target arrays. In one technique, absorption transients in the spectrum of a thin layer of molecules, termed an optical nanogauge, are investigated. Shock-induced molecular energy transfer processes are observed in condensed matter for the first time. In a second technique, sub-micron particles of an energetic material are shocked and probed using ps coherent Raman spectroscopy. This probing technique permits the instantaneous measurement of the temperature, pressure and composition of an energetic material under dynamic shock loading.
We present Rigid Field Hydrodynamic simulations of the magnetosphere of σ Ori E. We find that the X-ray emission from the star's magnetically confined wind shocks is very sensitive to the assumed mass-loss rate. To compare the simulations against the measured X-ray emission, we first disentangle the star from its recently discovered late-type companion using Chandra HRC-I observations. This then allows us to place an upper limit on the mass-loss rate of the primary, which we find to be significantly smaller than previously imagined.
The Magnetism in Massive Stars (MiMeS) Project is a consensus collaboration among many of the foremost international researchers of the physics of hot, massive stars, with the basic aim of understanding the origin, evolution and impact of magnetic fields in these objects. At the time of writing, MiMeS Large Programs have acquired over 950 high-resolution polarised spectra of about 150 individual stars with spectral types from B5-O4, discovering new magnetic fields in a dozen hot, massive stars. The quality of this spectral and magnetic matériel is very high, and the Collaboration is keen to connect with colleagues capable of exploiting the data in new or unforeseen ways. In this paper we review the structure of the MiMeS observing programs and report the status of observations, data modeling and development of related theory.