Agent-Based Team Aiding in a Time Critical Task

In this paper we evaluate the effectiveness of agent-based aiding in support of a time-critical team-planning task for teams of both humans and heterogeneous software agents. The team task consists of human subjects playing the role of military commanders and cooperatively planning to move their respective units to a common rendezvous point, given time and resource constraints. The objective of the experiment was to compare the effectiveness of agent-based aiding for individual and team tasks as opposed to the baseline condition of manual route planning. There were two experimental conditions: the Aided condition, where a Route Planning Agent (RPA) finds a least cost plan between the start and rendezvous points for a given composition of force units; and the Baseline condition, where the commanders determine initial routes manually, and receive basic feedback about the route. We demonstrate that the Aided condition provides significantly better assistance for individual route planning and team-based re-planning

Modulation of Neuronal Signal Transduction Systems by Extracellular ATP

The secretion of ATP by stimulated nerves is well documented. Following repetitive stimulation, extracellular ATP at the synapse can accumulate to levels estimated to be well over 100 Μ M. The present study examined the effects of extracellular ATP in the concentration range of 0.1–1.0 m M on second-messenger-generating systems in cultured neural cells of the clones NG108-15 and NIE-115. Cells in a medium mimicking the physiological extracellular environment were used to measure 45 Ca 2+ uptake, changes in free intracellular Ca 2+ levels by the probes aequorin and Quin-2, de novo generation of cyclic GMP and cyclic AMP from intracellular GTP and ATP pools prelabeled with [ 3 H]guanosine and [ 3 H]adenine, respectively, and phosphoinositide metabolism in cells preloaded with [ 3 H]inositol and assayed in the presence of LiCI. Extracelluar ATP induced a concentration-dependent increase of 45 Ca 2+ uptake by intact cells, which was additive with the uptake induced by K + depolarization. The increased uptake involved elevation of intracellular free Ca 2+ ions, evidenced by measuring aequorin and Quin-2 signals. At the same concentration range (0.1–1.0 m M ), extracellular ATP induced an increase in [ 3 H]cyclic GMP formation, and a decrease in prostaglandin E 1 -stimulated [ 3 H]cyclic AMP generation. In addition, extracellular ATP (1 m M ) caused a large (15-fold) increase in [ 3 H]inositol phosphates accumulation, and this effect was blocked by including La 3+ ions in the assay medium. In parallel experiments, we found in NG 108–15 cells surface protein phosphorylation activity that had an apparent K m for extracellular ATP at the same concentration required to produce half-maximal effects on Ca 2+ uptake. Extracellular ATP at concentrations that can be produced in the synaptic cleft by repetitive stimulation but not during routine transmission can thus initiate a unique chain of events, which may play a role in the induction of long-term adaptive changes in neuronal function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65952/1/j.1471-4159.1988.tb13263.x.pd

736–3 Costs and Complications of Non-thoracotomy Defibrillator Systems: Impact of Health Care Financing Administration Guidelines

Non-thoracotomy implantable defibrillator (ICD) systems have been shown to have lower costs and fewer complications than thoracotomy systems. Recent interpretation of Health Care Financing Administration regulations has challenged reimbursement for investigational devices or combinations of components not approved by the Food and Drug Administration (“off-label”). We compared the costs and complications associated with approved pulse generator/lead systems (CPI 1600/Endotak, CPl 1705/Endotak and Medtronic 7217/Transvene, n=136) with investigational and “off-label” systems (CPI 1625/Endotak, CPI 1715/Endotak, Medtronic 7219/Transvene and Ventritex V100 or V110/TVL and Vl00/Endotak, n=79). Age [63±12 years versus 63±11 years (mean±SD)] and ejection fraction (31±15% versus 31±11%) were similar for patients with approved and investigational systems, respectively. However, total hospital charges including preoperative care and evaluation, implant procedure and hardware, postoperative testing and revisions were $64±19,000 for approved devices versus$57±16,000 for non-approved devices (p=0.02) despite higher overall costs of newer pulse generators and leads. Total length of stay was 17±10 days versus 14±8 days (p=0.03) and complications including lead dislodgement, increased defibrillation threshold, hematoma and infection were 25/136 versus 4/77 (p<0.005) for approved and investigational or “off-label” systems, respectively. Based on data provided by the manufacturers, anticipated average battery longevity is 3.8 years for approved systems and 5.5 years for investigational or “off-label” systems.ConclusionsThe prudent use of current investigational or “off-label” nonthoracotomy ICD systems is more cost-effective and is associated with fewer complications than approved ICD systems. When increased battery longevity is considered, long term costs of non-thoracotomy ICD therapy may be improved dramatically with the use of investigational or “off-label” systems. Review of reimbursement regulations may be warranted

Ventricular septal defect associated with aneurysm of the membranous septum

The most common variety of ventricular septal defect, a perimembranous defect, is frequently associated with a so-called aneurysm of the membranous septum. Previous studies have suggested that ventricular septal defects associated with an aneurysm of the membranous septum tend to spontaneously decrease in size or close more than defects without such an aneurysm. To better define the natural history of this entity, clinical and catheterization data from 87 patients with ventricular septal defect and aneurysm of the membranous septum were reviewed. The initial evaluation was made at a median age of 0.3 years (range 0.1 to 11), with the final evaluation at a median age of 10 years (range 1.5 to 20) and a median duration of follow-up of 8.6 years (range 1.2 to 18.8).Approximately 75% of the ventricular septal defects had a small or no left to right shunt at last evaluation. Overall, 48 patients (55%) had no significant change in the size of the defect, and 39 (45%) showed improvement during the period of observation. Only four patients (5%) had spontaneous closure of the defect. Of the 49 patients who presented with a large left to right shunt, with or without congestive heart failure, 23 (47%) had persistence of a shunt large enough to warrant surgery. When spontaneous improvement occurred, it did so by 6 years of age in all but one patient. Therefore, a continued tendency for a ventricular septal defect associated with an aneurysm of the membranous septum to spontaneously decrease in size or close after this age may be less likely than previously suggested. The actual morphologic substrate of this entity usually consists of tricuspid valve tissue adherent to the edges of the ventricular septal defect

Computed tomography assessment of peripubertal craniofacial morphology in a sheep model of binge alcohol drinking in the first trimester

Identification of facial dysmorphology is essential for the diagnosis of fetal alcohol syndrome (FAS); however, most children with fetal alcohol spectrum disorders (FASD) do not meet the dysmorphology criterion. Additional objective indicators are needed to help identify the broader spectrum of children affected by prenatal alcohol exposure. Computed tomography (CT) was used in a sheep model of prenatal binge alcohol exposure to test the hypothesis that quantitative measures of craniofacial bone volumes and linear distances could identify alcohol-exposed lambs. Pregnant sheep were randomly assigned to four groups: heavy binge alcohol, 2.5 g/kg/day (HBA); binge alcohol, 1.75 g/kg/day (BA); saline control (SC); and normal control (NC). Intravenous alcohol (BA; HBA) or saline (SC) infusions were given three consecutive days per week from gestation day 4-41, and a CT scan was performed on postnatal day 182. The volumes of eight skull bones, cranial circumference, and 19 linear measures of the face and skull were compared among treatment groups. Lambs from both alcohol groups showed significant reduction in seven of the eight skull bones and total skull bone volume, as well as cranial circumference. Alcohol exposure also decreased four of the 19 craniofacial measures. Discriminant analysis showed that alcohol-exposed and control lambs could be classified with high accuracy based on total skull bone volume, frontal, parietal, or mandibular bone volumes, cranial circumference, or interorbital distance. Total skull volume was significantly more sensitive than cranial circumference in identifying the alcohol-exposed lambs when alcohol-exposed lambs were classified using the typical FAS diagnostic cutoff of ≤10th percentile. This first demonstration of the usefulness of CT-derived craniofacial measures in a sheep model of FASD following binge-like alcohol exposure during the first trimester suggests that volumetric measurement of cranial bones may be a novel biomarker for binge alcohol exposure during the first trimester to help identify non-dysmorphic children with FASD

Maternal choline supplementation in a sheep model of first trimester binge alcohol fails to protect against brain volume reductions in peripubertal lambs

Fetal alcohol spectrum disorder (FASD) is a leading potentially preventable birth defect. Poor nutrition may contribute to adverse developmental outcomes of prenatal alcohol exposure, and supplementation of essential micronutrients such as choline has shown benefit in rodent models. The sheep model of first-trimester binge alcohol exposure was used in this study to model the dose of maternal choline supplementation used in an ongoing prospective clinical trial involving pregnancies at risk for FASD. Primary outcome measures included volumetrics of the whole brain, cerebellum, and pituitary derived from magnetic resonance imaging (MRI) in 6-month-old lambs, testing the hypothesis that alcohol-exposed lambs would have brain volume reductions that would be ameliorated by maternal choline supplementation. Pregnant sheep were randomly assigned to one of five groups – heavy binge alcohol (HBA; 2.5 g/kg/treatment ethanol), heavy binge alcohol plus choline supplementation (HBC; 2.5 g/kg/treatment ethanol and 10 mg/kg/day choline), saline control (SC), saline control plus choline supplementation (SCC; 10 mg/kg/day choline), and normal control (NC). Ewes were given intravenous alcohol (HBA, HBC; mean peak BACs of ~280 mg/dL) or saline (SC, SCC) on three consecutive days per week from gestation day (GD) 4–41; choline was administered on GD 4–148. MRI scans of lamb brains were performed postnatally on day 182. Lambs from both alcohol groups (with or without choline) showed significant reductions in total brain volume; cerebellar and pituitary volumes were not significantly affected. This is the first report of MRI-derived volumetric brain reductions in a sheep model of FASD following binge-like alcohol exposure during the first trimester. These results also indicate that maternal choline supplementation comparable to doses in human studies fails to prevent brain volume reductions typically induced by first-trimester binge alcohol exposure. Future analyses will assess behavioral outcomes along with regional brain and neurohistological measures

Hypoxia Regulates BMP4 Expression in the Murine Spleen during the Recovery from Acute Anemia

Bone marrow erythropoiesis is primarily homeostatic, producing new erythrocytes at a constant rate. However at times of acute anemia, new erythrocytes must be rapidly produced much faster than bone marrow steady state erythropoiesis. At these times stress erythropoiesis predominates. Stress erythropoiesis occurs in the fetal liver during embryogenesis and in the adult spleen and liver. In adult mice, stress erythropoiesis utilizes a specialized population of stress erythroid progenitors that are resident in the spleen. In response to acute anemia, these progenitors rapidly expand and differentiate in response to three signals, BMP4, SCF and hypoxia. In absence of acute anemic stress, two of these signals, BMP4 and hypoxia, are not present and the pathway is not active. The initiating event in the activation of this pathway is the up-regulation of BMP4 expression in the spleen.In this paper we analyze the regulation of BMP4 expression in the spleen by hypoxia. Using stromal cell lines, we establish a role for hypoxia transcription factor HIFs (Hypoxia Inducible Factors) in the transcription of BMP4. We identified putative Hypoxia Responsive Elements (HREs) in the BMP4 gene using bioinformatics. Analysis of these elements showed that in vivo, Hif2alpha binds two cis regulatory sites in the BMP4 gene, which regulate BMP4 expression during the recovery from acute anemia.These data show that hypoxia plays a key role in initiating the BMP4 dependent stress erythropoiesis pathway by regulating BMP4 expression