Impact of Modular Total Absorption Spectrometer measurements of ß decay of fission products on the decay heat and reactor ν[over ¯]_{e} flux calculation.

We report the results of a ß-decay study of fission products ^{86}Br, ^{89}Kr, ^{89}Rb, ^{90gs}Rb, ^{90m}Rb, ^{90}Kr, ^{92}Rb, ^{139}Xe, and ^{142}Cs performed with the Modular Total Absorption Spectrometer (MTAS) and on-line mass-separated ion beams. These radioactivities were assessed by the Nuclear Energy Agency as having high priority for decay heat analysis during a nuclear fuel cycle. We observe a substantial increase in ß feeding to high excited states in all daughter isotopes in comparison to earlier data. This increases the average γ-ray energy emitted by the decay of fission fragments during the first 10 000 s after fission of ^{235}U and ^{239}Pu by approximately 2% and 1%, respectively, improving agreement between results of calculations and direct observations. New MTAS results reduce the reference reactor ν[over ¯]_{e} flux used to analyze reactor ν[over ¯]_{e} interaction with detector matter. The reduction determined by the ab initio method for the four nuclear fuel components, ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu, amounts to 0.976, 0.986, 0.983, and 0.984, respectively.

Clinical and microbiological implications of time-to-positivity of blood cultures in patients with Gram-negative bacilli bacteremia.

Time-to-positivity (TTP) is defined as the length of time from the beginning of culture incubation to the detection of bacterial growth by an automated system. The objective of this study was to assess the clinical and microbiological implications of TTP among patients with Gram-negative bacilli (GNB) bacteremia. This was a prospective, single-center, observational study. Patients aged 18 years or older with one or more blood cultures growing GNB were included and followed until hospital discharge or death. Patients were excluded if they were without symptoms of infection, if they had polymicrobial culture, or if the culture was positive with an obligate anaerobe. A multivariate logistic regression analysis was performed to determine the predictors of in-hospital mortality, including TTP (primary endpoint), demographics, disease severity, comorbidities, pathogen type, source of infection, time to symptom resolution, hospital/intensive care unit (ICU) length of stay, adequacy of empiric antibiotics, and presence of an extended-spectrum beta-lactamase (ESBL)-producing bacteria. One hundred consecutive patients with GNB bacteremia were enrolled. TTP was an independent predictor of mortality; for every hour that TTP was shorter, the risk of mortality increased by 10% [odds ratio (OR) 1.10, 95% confidence interval (CI) 1.00-1.21, p = 0.049]. Other predictors of mortality included severity of illness, ESBL-producing GNB, and ICU admission within 24 h before culture. Mortality was highest among patients with inadequate empiric therapy (56% vs. 14%, p < 0.001) and TTP <11 h (23.1% vs. 8.3%, p = 0.18). Lactose-fermenting GNB had a shorter mean TTP than non-lactose fermenters (11.4 vs. 17.9 h, p = 0.001). Among patients with bacteremia due to GNB, TTP values are inversely associated with mortality risk.

Distinct roles of neuroligin-1 and SynCAM1 in synapse formation and function in primary hippocampal neuronal cultures.

Neuroligins are a family of cell adhesion molecules critical in establishing proper central nervous system connectivity; disruption of neuroligin signaling in vivo precipitates a broad range of cognitive deficits. Despite considerable recent progress, the specific synaptic function of neuroligin-1 (NL1) remains unclear. A current model proposes that NL1 acts exclusively to mature pre-existent synaptic connections in an activity-dependent manner. A second element of this activity-dependent maturation model is that an alternate molecule acts upstream of NL1 to initiate synaptic connections. SynCAM1 (SC1) is hypothesized to function in this capacity, though several uncertainties remain regarding SC1 function. Using overexpression and chronic pharmacological blockade of synaptic activity, we now demonstrate that NL1 is capable of robustly recruiting synapsin-positive terminals independent of synaptic maturation and activity in 2-week old primary hippocampal neuronal cultures. We further report that neither SC1 overexpression nor knockdown of endogenous SC1 impacts synapsin punctum densities, suggesting that SC1 is not a limiting factor of synapse initiation in maturing hippocampal neurons in vitro. Consistent with these findings, we observed profoundly greater recruitment of synapsin-positive presynaptic terminals by NL1 than SC1 in a mixed-culture assay of artificial synaptogenesis between primary neurons and heterologous cells. Collectively, our results contend multiple aspects of the proposed model of NL1 and SC1 function and motivate an alternative model whereby SC1 may mature synaptic connections forged by NL1. Supporting this model, we present evidence that combined NL1 and SC1 overexpression triggers excitotoxic neurodegeneration through SC1 signaling at synaptic connections initiated by NL1.

Safety and efficacy of vaccination of seronegative bulls with modified-live, cytopathic bovine viral diarrhea viruses.

The objectives were to vaccinate peri-pubertal bulls with a modified-live vaccine consisting of cytopathic BVDV strains Singer and 296 and evaluate the resulting: (a) transient shed of modified-live, cytopathic BVDV in semen; (b) risk of prolonged testicular infection; and (c) protection against subsequent testicular infection due to viral challenge. Seronegative, peri-pubertal bulls were vaccinated subcutaneously with a standard dose of vaccine (n=11) or were maintained as unvaccinated controls (n=11). Forty-nine days after vaccination, all bulls were intranasally inoculated with a noncytopathic field strain of BVDV. Semen and testicular biopsies collected after vaccination and challenge were assayed for BVDV using virus isolation, reverse transcription-nested PCR, or immunohistochemistry, and the identity of viral strains was determined by nucleotide sequencing of PCR products. Vaccination of peri-pubertal bulls with this vaccine caused a short-term, transient shed of only the type 1a strain of modified-live, cytopathic BVDV in semen for up to 10d after vaccination. The vaccine did not cause prolonged testicular infection. Vaccination with this product prevented development of prolonged testicular infections after subsequent exposure to a field strain of BVDV.

Diet and reproduction in the Australian butterfly ray Gymnura australis from northern and north-eastern Australia.

The diet of Gymnura australis was dominated by teleosts (99.8% index of relative importance). A wide-ranging species, females matured at 446 mm disc width (W(D)), had a single functional ovary and two functional uteri. Males matured at 377 mm W(D) and had a single functional testis.

Performance of AlGaN/GaN high electron mobility transistors at nanoscale gate lengths.

The DC and RF performance of AlGaN/GaN high electron mobility transistors with nanoscale gate lengths is presented. The layer structures were grown by either metal organic chemical vapor deposition or rf plasma-assisted molecular beam epitaxy. Excellent scaling properties were observed as a function of both gate length and width and confirm that these devices are well suited to both high speed switching and power microwave applications.

The relative importance of task and contextual performance dimensions to supervisor judgments of overall performance.

Although evidence supports the unique contribution of task performance and contextual performance to overall evaluations, little is known about the relative contribution that specific dimensions of contextual performance make to overall performance judgments. This study evaluated the extent to which supervisors consider task and contextual performance by using relative weights (J. W. Johnson, 2000) to statistically describe the relative importance of specific dimensions of each type of performance to overall performance ratings. Within each of 8 job families in a large organization, each of 4 dimensions of contextual performance made not only a unique contribution but a relatively important contribution to the overall evaluation. Evidence also supports the adaptive performance dimension of handling work stress as an aspect of contextual performance and job-task conscientiousness as an aspect of both task and contextual performance.

A synthetic validity approach to testing differential prediction hypotheses.

A new method is presented for conducting differential prediction analyses that makes it possible to test differential prediction hypotheses with adequate statistical power even when the sample size within a job or a job family is very small. This method, called synthetic differential prediction analysis, represents an application of the logic of synthetic validation to differential prediction analyses. The authors explain this new method and describe its application in a selection-system validation study conducted in a large organization.

Evolution in damage control for exsanguinating penetrating abdominal injury.

OBJECTIVE: Damage control (DC) has proven valuable in exsanguinated patients. The purpose of this study was to quantify and qualify the impact of current damage control principles applied in a penetrating abdominal injury (PAI) population. METHODS: Over a 3-year period (June 1997-May 2000), of 271 laparotomies for PAI, 24 patients underwent DC (8.9%). Demographics, injury grade, resuscitative and operative parameters, acid-base status, coagulation profiles, fluid/transfusion requirements, definitive repairs, abdominal closure, complications, and outcomes were reviewed. Data were compared with our DC experience a decade earlier. Fisher's exact test was used for comparisons. RESULTS: Overall survival improved for equivalent Injury Severity Score, Revised Trauma Score, TRISS, admission systolic blood pressure, operating room systolic blood pressure, and Penetrating Abdominal Trauma Index score. Solids (1.2 vs. 1.3), hollow organ (1.5 vs. 1.7), and major vascular injuries (0.5 vs. 0.8) per patient remain unchanged. Currently, there was less hypothermia with equivalent operating room times. In intensive care unit survivors, acid-base status was similar but coagulopathy and hypothermia were less severe. Definitive colon management has shifted from ostomies to anastomoses. Eventual fascial closure occurred in 14 of 19 (74%) compared with 12 of 14 (86%) in the historical group. There were three gastrointestinal fistulae (one pancreatic), one anastomotic leak, and three intra-abdominal abscesses. CONCLUSION: Continued application of DC principles has led to improved survival with PAI. Better control of temperature, experience with the open abdomen, and intensive care unit care may be causative.

Correlation of head-to-body delivery intervals in shoulder dystocia and umbilical artery acidosis.

OBJECTIVE: Our goal was to determine the effect of shoulder dystocia on umbilical artery acidosis. STUDY DESIGN: We performed a retrospective analysis of 134 mother-infant pairs of shoulder dystocia cases at our institution from January 1, 1994, through December 31, 1997. Cases were identified from the obstetric database, and charts were abstracted for demographics, head-to-body delivery interval, umbilical blood gas parameters, and neonatal outcome. Pooled student t tests were used to compare mean blood gas values with data previously reported from our patient population. Regression analysis was performed regarding head-to-body delivery interval and blood gas parameters. RESULTS: The mean umbilical artery pH of shoulder dystocia cases (7.23 +/-.082) was less than the mean arterial pH of all vaginal deliveries in our institution (7.27 +/-.069), P <.001. Head-to-body delivery intervals (available for 44 cases) were not associated with statistically significant alterations in umbilical artery pH (r(2) =.0004), PCO(2) (r(2) =.011), or base deficit (r(2) =.006). Increasing head-to-body delivery interval was also not significantly correlated with decreasing 5-minute Apgar score (r =.0278). CONCLUSION: In our study population, shoulder dystocia resulted in statistically significant but clinically insignificant reductions in mean umbilical artery blood gas parameters. No statistically significant linear relationship was identified between the head-to-body delivery interval and fetal acid-base status.

Free intracellular Mg(2+) concentration and inhibition of NMDA responses in cultured rat neurons.

1. Intracellular Mg(2+) (Mg(2+)(i)) blocks single-channel currents and modulates the gating kinetics of NMDA receptors. However, previous data suggested that Mg(2+)(i) inhibits whole-cell current less effectively than predicted from excised-patch measurements. We examined the basis of this discrepancy by testing three hypothetical explanations. 2. To test the first hypothesis, that control of free Mg(2+)(i) concentration ([Mg(2+)](i)) during whole-cell recording was inadequate, we measured [Mg(2+)](i) using mag-indo-1 microfluorometry. The [Mg(2+)](i) measured in cultured neurons during whole-cell recording was similar to the pipette [Mg(2+)] measured in vitro, suggesting that [Mg(2+)](i) was adequately controlled. 3. To test the second hypothesis, that open-channel block by Mg(2+)(i) was modified by patch excision, we characterised the effects of Mg(2+)(i) using cell-attached recordings. We found the affinity and voltage dependence of open-channel block by Mg(2+)(i) similar in cell-attached and outside-out patches. Thus, the difference between Mg(2+)(i) inhibition of whole-cell and of patch currents cannot be attributed to a difference in Mg(2+)(i) block of single-channel current. 4. The third hypothesis tested was that the effect of Mg(2+)(i) on channel gating was modified by patch excision. Results of cell-attached recording and modelling of whole-cell data suggest that the Mg(2+)(i)-induced stabilisation of the channel open state is four times weaker after patch excision than in intact cells. This differential effect of Mg(2+)(i) on channel gating explains why Mg(2+)(i) inhibits whole-cell NMDA responses less effectively than patch responses.

Persistent activation of ERK contributes to glutamate-induced oxidative toxicity in a neuronal cell line and primary cortical neuron cultures.

Oxidative stress can trigger neuronal cell death and has been implicated in several chronic neurological diseases and in acute neurological injury. Oxidative toxicity can be induced by glutamate treatment in cells that lack ionotrophic glutamate receptors, such as the immortalized HT22 hippocampal cell line and immature primary cortical neurons. Previously, we found that neuroprotective effects of geldanamycin, a benzoquinone ansamycin, in HT22 cells were associated with a down-regulation of c-Raf-1, an upstream activator of the extracellular signal-regulated protein kinases (ERKs). ERK activation, although often attributed strictly to neuronal cell survival and proliferation, can also be associated with neuronal cell death that occurs in response to specific insults. In this report we show that delayed and persistent activation of ERKs is associated with glutamate-induced oxidative toxicity in HT22 cells and immature primary cortical neuron cultures. Furthermore, we find that U0126, a specific inhibitor of the ERK-activating kinase, MEK-1/2, protects both HT22 cells and immature primary cortical neuron cultures from glutamate toxicity. Glutamate-induced ERK activation requires the production of specific arachidonic acid metabolites and appears to be downstream of a burst of reactive oxygen species (ROS) accumulation characteristic of oxidative stress in HT22 cells. However, inhibition of ERK activation reduces glutamate-induced intracellular Ca(2+) accumulation. We hypothesize that the precise kinetics and duration of ERK activation may determine whether downstream targets are mobilized to enhance neuronal cell survival or ensure cellular demise.

Inhibition by intracellular Mg(2+) of recombinant N-methyl-D-aspartate receptors expressed in Chinese hamster ovary cells.

Intracellular Mg(2+) (Mg(i)(2+)) inhibits the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors in cultured cortical neurons. To examine the effects of Mg(i)(2+) on recombinant NMDA receptors composed of subunit combinations found in cortical neurons, we expressed heteromeric receptors composed of NR1/NR2A and of NR1/NR2B subunits in Chinese hamster ovary (CHO) cells. We recorded whole-cell currents from the recombinant receptors in the absence and presence of Mg(i)(2+). The voltage dependence of control (0 Mg(i)(2+)) NMDA-activated currents obtained from CHO cells transfected with NR1/NR2A and with NR1/NR2B receptors showed outward rectification, a property that has been observed previously in native cortical NMDA receptors. The magnitude and voltage dependence of inhibition by Mg(i)(2+) of NMDA-activated currents were similar in CHO cells transfected with NR1/NR2A receptors, CHO cells transfected with NR1/NR2B receptors, and in cultured neurons expressing native NMDA receptors. These observations suggest that Mg(i)(2+) has uniform effects on the native NMDA receptors expressed in cortical neurons. Furthermore, inhibition by Mg(i)(2+) must not depend on intracellular factors or post-translational receptor modifications that are specific to neurons. Finally, the results indicate that the previously observed differences between whole-cell and outside-out patch measurements of Mg(i)(2+) inhibition could not result from poor control of voltage or Mg(i)(2+) concentration in the dendrites of neurons. The most likely alternative explanation is that patch excision causes an alteration in NMDA receptors that results in more effective inhibition by Mg(i)(2+).

A Heuristic Method for Estimating the Relative Weight of Predictor Variables in Multiple Regression.

The relative weight of predictor variables in multiple regression is difficult to determine because of non-zero predictor intercorrelations. Relative weight (also called relative importance by some researchers) is defined here as the proportionate contribution each predictor makes to R2, considering both its unique contribution and its contribution when combined with other variables. Although there are no unambiguous measures of relative weight when variables are correlated, some measures have been shown to provide meaningful results (Budescu, 1993; Lindeman, Merenda, & Gold, 1980). These measures are very difficult to implement, however, when the number of predictors is greater than about five. A method is proposed that is computationally efficient with any number of predictors, and is shown to produce results that are very similar to those produced by more complex methods. Recommendations are made for when this procedure may be applied and in what situations it is not appropriate.

Permeant ion regulation of N-methyl-D-aspartate receptor channel block by Mg(2+).

Block of the channel of N-methyl-D-aspartate (NMDA) receptors by external Mg(2+) (Mg(o)(2+)) has broad implications for the many physiological and pathological processes that depend on NMDA receptor activation. An essential property of channel block by Mg(o)(2+) is its powerful voltage dependence. A widely cited explanation for the strength of the voltage dependence of block is that the Mg(o)(2+)-binding site is located deep in the channel of NMDA receptors; Mg(o)(2+) then would sense most of the membrane potential field during block. However, recent electrophysiological and mutagenesis studies suggest that the blocking site cannot be deep enough to account for the voltage dependence of Mg(o)(2+) block. Here we describe the basis for this discrepancy: the magnitude and voltage dependence of channel block by Mg(o)(2+) are strongly regulated by external and internal permeant monovalent cations. Our data support a model in which access to the channel by Mg(o)(2+) is prevented when permeant ion-binding sites at the external entrance to the channel are occupied. Mg(o)(2+) can block the channel only when the permeant ion-binding sites are unoccupied and then can either unblock back to the external solution or permeate the channel. Unblock to the external solution is prevented if external permeant ions bind while Mg(2+) blocks the channel, although permeation is still permitted. The model provides an explanation for the strength of the voltage dependence of Mg(o)(2+) block and quantifies the interdependence of permanent and blocking ion binding to NMDA receptors.

Corrosion of stainless steel, nickel-titanium, coated nickel-titanium, and titanium orthodontic wires.

Orthodontic wires containing nickel have been implicated in allergic reactions. The potential for orthodontic wires to cause allergic reactions is related to the pattern and mode of corrosion with subsequent release of metal ions, such as nickel, into the oral cavity. The purpose of this study was to determine if there is a significant difference in the corrosive potential of stainless steel, nickel titanium, nitride-coated nickel titanium, epoxy-coated nickel titanium, and titanium orthodontic wires. At least two specimens of each wire were subjected to potentiostatic anodic dissolution in 0.9% NaCl solution with neutral pH at room temperature. Using a Wenking MP 95 potentiostat and an electrochemical corrosion cell, the breakdown potential of each wire was determined. Photographs were taken of the wire speci mens using a scanning electron microscope, and surface changes were qualitatively evaluated. The breakdown potentials of stainless steel, two nickel titanium wires, nitride-coated nickel titanium, epoxy-coated nickel titanium, and titanium were 400 mV, 300 mV, 750 mV, 300 mV, 1800 mV, and >2000 mV, respectively. SEM photographs revealed that some nickel titanium and stainless steel wires were susceptible to pitting and localized corrosion. The results indicate that corrosion occurred readily in stainless steel. Variability in breakdown potential of nickel titanium alloy wires differed across vendors' wires. The nitride coating did not affect the corrosion of the alloy, but epoxy coating decreased corrosion. Titanium wires and epoxy-coated nickel titanium wires exhibited the least corrosive potential. For patients allergic to nickel, the use of titanium or epoxy-coated wires during orthodontic treatment is recommended.

Comparison of results in two implantable defibrillators. Jewel 7219D Investigators.

The Jewel 7219D was the first non-thoracotomy implantable cardioverter-defibrillator (ICD) with biphasic shock capability small enough to be placed in the prepectoral subcutaneous position. Size reduction of ICDs is desirable, but safety and efficacy of smaller devices must be demonstrated. Outcomes of patients treated with the Jewel 7219D defibrillator (n = 1,781) and with its precursor model PCD 7217B (n = 2,637) were compared. To use PCD patients (n = 2,637) as historical (n = 2,574) and concurrent controls (n = 63), statistical adjustments using the Cox proportional-hazards regression model were made. Jewel recipients (n = 1,781) treated in 106 US and 32 non-US centers exhibited similar characteristics including a mean age of 59 years, 78% men, ejection fraction of 34%, history of aborted sudden cardiac death in 41%, and coronary artery disease in 70%. Implantation was completed in 1,777 of 1,781 (99.9%) attempts and success with the first electrode configuration and polarity was 89.5%. Kaplan-Meier cumulative first-year survivals for cardiac and all-cause mortality were 98.5% and 93.3%. Complication-free first-year survival for Jewel implants in prepectoral subcutaneous (n = 582), subpectoral submuscular (n = 366), and abdominal (n = 449) positions did not differ (p > 0.05). First-year survival free of pocket-related complications exceeded 98% in all locations. Adjusted cardiac and all-cause first-year mortality, and efficacy in terminating spontaneous tachyarrhythmias did not differ between the 2 device groups. In conclusion, the safety and efficacy of Jewel model 7219D in the prepectoral subcutaneous position are at least equal to either those of Jewel models implanted in different positions or to those of the previously extensively characterized PCD 7217B.

Physical and comparative mapping of distal mouse chromosome 16. 5 p5.

Distal mouse Chromosome 16 (Chr. 16) includes a region of conserved linkage with human Chromosome 21 (Chr. 21). Mouse models of Down syndrome based on trisomy of distal Chr. 16 have several phenotypes similar to those seen in human patients and have proven useful for correlating dosage imbalance of specific genes with specific developmental anomalies. The degree to which such findings can be related to Down syndrome depends on how well the conserved synteny is maintained. Twenty-four genes have been mapped in both species and there are no discordancies, but the region could carry hundreds of genes. Comparative sequence represents the ultimate comparative map and will aid in identification of genes and their regulatory sequences. A physical map of the distal 4.5 Mb of Chr. 16 has been assembled as an essential step toward a map of sequence-ready templates. The map consists of 51 YACs and 15 BACs and includes 18 transcripts, 9 of which are mapped for the first time in mouse, and 3 of which are, for the first time, described in either species. YAC fragmentation was used to precisely localize the 49 markers on the map. Comparison of this physical map with that of the corresponding region on Chr. 21 shows conservation not only of gene order but of size in the 3 Mb from Cbr1 to Ets2; distal to Ets2, the human map is expanded.