SEARCH · PubMed Health

Results for “Predictive modeling”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,135 records · Page 63Linked to original sources

PubMed2005

A predictive model for the level of sIgA based on IgG levels following the oral administration of antigens expressed in Saccharomyces cerevisiae.

Oral vaccination may be the most efficient way of inducing an immune response at the remote mucosal site through the common mucosal immune network. Antigen-specific secretory IgA (sIgA) is the major immunoglobulin type generally detected in the secretions of experimental animals following an effective oral immunization. Actinobacillus pleuropneumoniae causing disease in the lung of pig initially interacts, colonizes, and infects the host tissues at the mucosal surface of the respiratory tract. Also, importantly for A. pleuropneumoniae protection, the quantity of sIgA in the lung had merits associated with the mucosal immunity. However, there is no simple method to monitor the level of sIgA as an indicator for the induction of local immune responses by an oral vaccination in the target tissue. Therefore, the relationship between sIgA and IgG was analyzed to evaluate the induction of local immune responses by an oral immunization with Saccharomyces cerevisiae expressing the apxIA and apxIIA genes of A. pleuropneumoniae in this study. The correlation coefficient of determination (r2 x 100) for paired samples in both vaccinated and control groups showed a significant positive-relationship between IgG in sera and sIgA in the lung or intestine. These results indicated that IgG antibody titers in sera could be useful to indirectly predict local immune response, and sIgA, in the lung or intestine to evaluate the efficacy of an oral vaccination.

Actinobacillus pleuropneumoniae↗

PubMed2003

Use of time-temperature integrators and predictive modeling to evaluate microbiological quality loss in poultry products.

The purpose of this study was to characterize the kinetics of the spoilage process of chicken drumsticks in order to evaluate the application of an enzyme process-based time-temperature integrator (TTI) as a continuous quality monitor of poultry products. Shelf life studies were conducted at several temperatures (3 to 20 degrees C) to characterize (i) the poultry spoilage process as a function of total aerobic bacteria and Pseudomonas species populations and (ii) the TTI chroma response function. Two types of poultry products were examined: ice-packed and chill-packed drumsticks. An enzyme-based TTI with a color change response from green to yellow was used. Activation energies for each of the poultry products and each of the bacterial populations were as follows: 21.8 +/- 1.6 kcal/mol (ca. 91.2 +/- 6.7 kJ/mol) for ice-packed drumsticks and total aerobic population, 18.8 +/- 4.5 kcal/mol ca. 78.7 +/- 18.8 kJ/mol) for ice-packed drumsticks and Pseudomonas spp., 17.0 +/- 2.3 kcal/mol (ca. 71.1 +/- 9.6 kJ/mol) for chill-packed drumsticks and total aerobic population, and 14.1 +/- 3.6 kcal/mol (ca. 59.0 +/- 15.1 kJ/mol) for chill-packed drumsticks and Pseudomonas spp. The activation energy calculated for the TTI, 19.1 +/- 1.8 kcal/mol (ca. 79.9 +/- 7.5 kJ/mol), was determined to be adequately close to that of the poultry spoilage process to make effective quality predictions possible. Initial bacteria levels on the chicken drumsticks were uniform and not judged as important limiting factors in the application of TTIs to poultry products. Because the poultry spoilage process was reasonably characterized on the basis of Arrhenius kinetics, there is further need to conduct validation studies to determine the ability of TTIs to provide a continuous quality monitoring system.

Animals↗

PubMedDate not supplied

Measured concentrations of herbicides and model predictions of atrazine fate in the Patuxent River estuary.

The environmental fate of herbicides in estuaries is poorly understood. Estuarine physical transport processes and the episodic nature of herbicide release into surface waters complicate interpretation of water concentration measurements and allocation of sources. Water concentrations of herbicides and two triazine degradation products (CIAT [6-amino-2-chloro-4-isopropylamino-s-triazine] and CEAT [6-amino-2-chloro-4-ethylamino-s-triazine]) were measured in surface water from four sites on 40 d from 4 Apr. through 29 July 19% in the Patuxent River estuary, part of the Chesapeake Bay system. Atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) was most persistent and present in the highest concentrations (maximum = 1.29 microg/L). Metolachlor [2-chloro-6'-ethyl-N-(2-methoxy-1-methylethyl)-o-acetoluidide], CIAT, CEAT, and simazine (1-chloro-3,5-bisethylamino-2,4,6-triazine) were frequently detected with maximum concentration values of 0.61, 1.1, 0.76, and 0.49 microg/L, respectively. A physical transport model was used to interpret atrazine concentrations in the context of estuarine water transport, giving estimates of in situ degradation rates and total transport. The estimated half-life of atrazine in the turbid, shallow upper estuary was t(1/2) = 20 d, but was much longer (t(1/2) = 100 d) in the deeper lower estuary. Although most (93%) atrazine entered the estuary upstream via the river, simulations suggested additional inputs directly to the lower estuary. The total atrazine load to the estuary from 5 April to 15 July was 71 kg with 48% loss by degradation and 31% exported to the Chesapeake Bay. Atrazine persistence in the estuary is directly related to river flows into the estuary. Low flows will increase atrazine residence time in the upper estuary and increase degradation losses.

Atrazine↗

PubMed2005

A selective allosteric potentiator of metabotropic glutamate (mGlu) 2 receptors has effects similar to an orthosteric mGlu2/3 receptor agonist in mouse models predictive of antipsychotic activity.

Recent studies suggest that agonists of group II metabotropic glutamate (mGlu) receptors (mGlu2/3) have potential utility as novel therapeutic agents for treatment of psychiatric disorders such as anxiety and schizophrenia. Agonists of mGlu2/3 receptors block amphetamine- and phencyclidine (PCP)-induced hyperlocomotor activity in rodents, two actions that may predict potential antipsychotic activity of these compounds. We now report that LY487379 [N-(4-(2-methoxyphenoxy)phenyl)-N-(2,2,2-trifluoroethylsulfonyl)pyrid-3-ylmethylamine], a recently described selective allosteric potentiator of mGlu2 receptor, has behavioral effects similar to mGlu2/3 receptor agonists. LY487379 and LY379268 [(-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate], an ortho-steric mGlu2/3 receptor agonist, induced similar dose-dependent reductions in PCP- and amphetamine-induced hyperlocomotor activity in C57BL6/J mice at doses that did not significantly alter spontaneous locomotor activity. These effects were blocked by the mGlu2/3 receptor antagonist LY341495 [(2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid]. LY487379 had a short duration of action compared with LY379268. Furthermore, unlike the mGlu2/3 agonist, LY487379 reversed amphetamine-induced disruption of prepulse inhibition of the acoustic startle reflex. When LY379268 was given chronically, it failed to block amphetamine- and PCP-induced hyperlocomotor activity. The finding that the effects of an orthosteric mGlu2/3 receptor agonist in these models can be mimicked by a selective allosteric potentiator of mGlu2 suggests that these effects are mediated by the mGlu2 receptor subtype. Furthermore, these data raise the possibility that a selective allosteric potentiator of mGlu2 receptor could have utility as a novel approach for the treatment of schizophrenia.

Allosteric Regulation↗

PubMed2003

Modifiable behavioral factors in a biopsychosocial model predict inadequate and excessive gestational weight gain.

OBJECTIVE: The research addresses two questions: Are potentially modifiable psychosocial and behavioral factors related to gestational weight gain? Do the same factors relate to both excessive and insufficient weight gain? DESIGN: Prospective cohort study that followed women from early pregnancy until two years postpartum. Data were collected through mailed questionnaires and an audit of the medical record. Subjects/setting The sample included 622 healthy adult women who gave birth to live singleton infants. Subjects were recruited from all women who registered for prenatal care in a hospital and primary care clinic system serving a 10-county area of Upstate New York. Statistical analyses performed Multiple linear and logistic regression with adjustment for timing of measurements and length of gestation were performed. RESULTS: Only 38% of women gained an amount of weight in pregnancy that was within the range recommended by the Institute of Medicine. Valid and easily implemented measures of change in food intake and physical activity from prepregnancy and cigarette smoking during pregnancy were each significantly (P<.05) and independently related to gestational weight gain. Along with other variables in a biopsychosocial regression model, these variables accounted for 27% of the variance in gestational weight gain and were also significantly related to risk of inadequate and excessive gain. APPLICATIONS/CONCLUSIONS: The findings facilitate the design of more effective nutrition interventions to promote appropriate gestational weight gain and the long-term health of women and their infants.

Adaptation, Psychological↗

PubMedDate not supplied

Frost injury prediction model for Douglas-fir seedlings in the Pacific Northwest.

Because simple seed- or breeding-zone guidelines are inadequate for controlling the risk of maladaptation to environmental stresses, we are developing operational procedures to assess the risk of frost kill to genetically improved families of Douglas-fir (Pseudotsuga menziesii Mirb. Franco). We have (1) determined the time course of cold hardening and dehardening of nursery-grown Douglas-fir seedlings over four winters, by means of controlled freezing tests, (2) fitted curves to relationships between temperature sum and both fall cold hardening and spring dehardening, (3) applied the temperature sum models to daily temperature records of 80 weather stations to estimate frequency of years with significant frost kill at those stations, (4) interpolated frost kill probabilities for tree farms, using a thin plate spline procedure with elevation, latitude and longitude as variables, and (5) prepared a coarse-scale frost risk map from the resulting grid point estimates. With the exception of a few high-elevation stations, the most damaging frost at any station in any year occurred in either the fall (October and November) or late spring (mid-April to mid-May). In general, damaging spring frosts were two to three times more frequent than fall frosts, and areas in Oregon were at greater risk than areas at similar elevations and longitudes further north. The spline surface was less precise for predicting spring frost risk than fall frost risk.

Journal Article↗

PubMed1997

A predictive model of the health benefits and cost effectiveness of celiprolol and atenolol in primary prevention of cardiovascular disease in hypertensive patients.

This study compares the antihypertensive and lipid modifying effects of treatment of mild to moderate hypertension with celiprolol or atenolol. It also models the 5-year cardiovascular risk reduction and the cost effectiveness of monotherapy from a partial societal perspective. The effects of celiprolol and atenolol on systolic blood pressure (SBP), total serum cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were obtained from a pooled analysis of published studies. Although celiprolol and atenolol had similar effects on SBP, celiprolol reduced the ratio of TC to HDL-C by 10.2% [95% confidence intervals (95% CI) -16.4%, -4.0%) but atenolol increased the ratio by 7.7% (95% CI of 3.4%, 12.0%). The 5-year absolute risks of an initial coronary or cerebrovascular event or cardiovascular death were computed for cohorts of patients treated with either agent or remaining untreated, using an accelerated failure time (AFT) model, based on Framingham Heart Study data. Inputs to the model were age, gender, smoking status, SBP, TC and HDL-C. The change in absolute risk was estimated using the changes in SBP and TC: HDL-C obtained from the pooled analysis. Average life-months gained by therapy were computed as differences between the Kaplan-Meier survival curves estimated from the model plus differences in 5-year cardiovascular death rates multiplied by average life expectancy obtained from life tables. Direct medical costs included drug treatment, and the costs of acute care for initial coronary and cerebrovascular events deferred by therapy over the 5-year treatment period. The model shows that in the lowest-risk base case (60-year-old men who are nondiabetic and nonsmokers with SBP of 160 mm Hg and a 5-year absolute cardiovascular risk of 12%), celiprolol (271 mg/day) is 2-fold more effective than atenolol (77.4 mg/day) in reducing coronary event risk, and equally effective in reducing cerebrovascular event risk. The number of individuals that would have to be treated for 5 years to avoid 1 coronary event is about 30 for celiprolol versus 70 for atenolol. Therapy with celiprolol yields more life-months and at current prices, the cost per life-year gained by therapy is significantly lower. Both drugs are cost effective by international standards in the treatment of patients with 5-year absolute cardiovascular risk greater than 10%, and are more cost effective in those patients at higher levels of absolute cardiovascular risk. The direct medical costs of treatment for 5 years with celiprolol are the same or slightly less than treatment with atenolol at the dosages used in the clinical trials, despite a 19% higher tablet price. Both drugs are more cost effective in patients at higher levels of absolute cardiovascular risk. These findings are sensitive to the drug dosages, tablet prices and the discount rate. Based on epidemiological and clinical data, replacing atenolol with celiprolol in patients with mild to moderate hypertension, but without overt cardiovascular disease, is predicted to have similar effects on stroke risk, but to be substantially more effective in reducing the risk of coronary events at no additional direct medical cost over a 5-year treatment period.

Adrenergic beta-Antagonists↗

PubMed2005

Model predictive glycaemic regulation in critical illness using insulin and nutrition input: a pilot study.

Stress-induced hyperglycaemia is prevalent in intensive care, impairing the immune response. Nutritional support regimes with high glucose content further exacerbate the problem. Tight glucose control has been shown to reduce mortality by up to 43% if levels are kept below 6.1 mmol/L. This research develops a control algorithm with insulin and nutritional inputs for targeted glucose control in the critically ill. Ethics approval for this research was granted by the Canterbury Ethics Committee. Proof-of-concept clinical pilot trials were conducted on intubated, insulin-dependent Christchurch ICU patients (n=7) on constant nutritional support. A target 10-15% reduction in glucose level per hour for a desired glucose level of 4-6 mmol/L was set. 43% and 91% of glucose targets were achieved within +/-5 and +/-20%, respectively. The mean error was 8.9% (0.5 mmol/L), with an absolute range [0, 2.9] mmol/L. End glucose levels were 40% lower compared to initial values. All large target errors are attributable to sudden changes in patient physiology at low glucose values, rather than systemic deficiencies. Target errors are consistent with and explainable by published sensor error distributions. The results show that intensive model-based glucose management with nutrition control reduced absolute glucose levels progressively while reducing the severity of glycaemic fluctuation even with significant inter-patient variability and time-varying physiological condition. Trials spanning longer periods of time are in development to verify the short-term pilot studies performed and to test the adaptability of the controller. Clinically, these results indicate potential in clinical use to reduce ICU mortality as well as reduce risk of severe complications.

Aged↗

PubMedDate not supplied

Using in vitro prediction models instead of the rabbit eye irritation test to classify and label new chemicals: a post hoc data analysis of the international EC/HO validation study.

The international validation study on alternative methods to replace the Draize rabbit eye irritation test, funded by the European Commission (EC) and the British Home Office (HO), took place during 1992-1994, and the results were published in 1995. The results of this EC/HO study are analysed by employing discriminant analysis, taking into account the classification of the in vivo data into eye irritation classes A (risk of serious damage to eyes), B (irritating to eyes) and NI (non-irritant). A data set for 59 test items was analysed, together with three subsets: surfactants, water-soluble chemicals, and water-insoluble chemicals. The new statistical methods of feature selection and estimation of the discriminant functions classification error were used. Normal distributed random numbers were added to the mean values of each in vitro endpoint, depending on the observed standard deviations. Thereafter, the reclassification error of the random observations was estimated by applying the fixed function of the mean values. Moreover, the leaving-one-out cross-classification method was applied to this random data set. Subsequently, random data were generated r times (for example, r = 1000) for a feature combination. Eighteen features were investigated in nine in vitro test systems to predict the effects of a chemical in the rabbit eye. 72.5% of the chemicals in the undivided sample were correctly classified when applying the in vitro endpoints lgNRU of the neutral red uptake test and lgBCOPo5 of the bovine opacity and permeability test. The accuracy increased to 80.9% when six in vitro features were used, and the sample was subdivided. The subset of surfactants was correctly classified in more than 90% of cases, which is an excellent performance.

Animal Testing Alternatives↗

PubMed2002

A competitive interaction model predicts the effect of WAY-100,635 on the time course of R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin-induced hypothermia.

The objective of this investigation was to characterize quantitatively the pharmacodynamic interaction between N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohexanecarboxamide (WAY-100,635) and R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin (R-8-OH-DPAT) in vivo. The 8-OH-DPAT-induced change in body temperature was used as a pharmacodynamic endpoint. Four groups of rats each received 1 mg/kg 8-OH-DPAT in 5 min during computer-controlled infusions of physiological saline or WAY-100,635, targeted at steady-state concentrations of 20, 85, and 170 ng/ml. Body temperature was monitored continuously with a telemetric system, and frequent blood samples were obtained to determine the pharmacokinetics of both drugs. Large differences in pharmacokinetics were observed between WAY-100,635 and R-8-OH-DPAT, reflected in values of the terminal elimination half-life of 33 and 143 min, respectively. Infusion of WAY-100,635 had no influence on the pharmacokinetics of R-8-OH-DPAT. With regard to the pharmacodynamics, clear antagonism of the R-8-OH-DPAT-induced hypothermia was observed. The complex pharmacological effect versus time profiles of R-8-OH-DPAT were analyzed on the basis of an indirect physiological response model with set point control coupled to a competitive interaction model for an agonist and antagonist acting at a common receptor. This model converged, yielding precise estimates of the pharmacodynamic parameters of both WAY-100,635 and R-8-OH-DPAT, which were independent of the infusion rate of WAY-100,635. The estimated in vivo binding constant of WAY-100,635 was 0.98 ng/ml (2.3 nM), which is very similar to the reported value from in vitro receptor binding assays. The findings of this investigation show that, in contrast to earlier reports in the literature, WAY 100,635 behaves as a pure competitive antagonist at the 5-hydroxytryptamine(1A) receptor in vivo.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2001

The lack of vasoconstrictor effect of the pineal hormone melatonin in an animal model predictive of antimigraine activity.

The pineal hormone, melatonin, has been implicated in the pathophysiology of migraine and several studies have demonstrated its vasoconstrictor properties. In the present study, systemic and carotid haemodynamic effects of melatonin, administered directly into the carotid artery, were investigated in anaesthetized pigs. Ten-minute intracarotid infusions of melatonin (1, 10 and 100 microg kg(-1) min(-1)) produced slight decreases in blood pressure and total carotid and arteriovenous anastomotic blood flows, but nutrient blood flow was not affected. The decrease in carotid blood flow was entirely caused by the hypotension, since no changes in vascular conductance values were observed. It is concluded that melatonin itself is not capable of producing vasoconstriction in the cranial circulation of anaesthetized pigs. Thus, it appears that melatonin has no anti-migraine potential via a vasoconstrictor mechanism.

Animals↗

PubMed2004

Clinical evaluation of a computer simulated prediction model of contrast enhancement of the liver in spiral CT.

OBJECTIVE: A software program was developed simulating a compartmental model of blood circulation based on differential equations. The aim of this study was to compare software-simulated levels of hepatic enhancement with the true values in patients and to test how many patients reach the simulated hepatic enhancement level. METHODS: As software program the CT application software carebolus 2 (Siemens, Forchheim, Germany) was used. Hepatic contrast-enhancement curves were simulated prior to CT examinations to evaluate a patient specific time delay after contrast application. At the time delay, when the simulation curve showed an enhancement threshold of 40 Hounsfield Units (HU), the CT spiral scan was started applying 120 ml contrast media with 2 ml/s. The simulated curves were compared with the empiric curves of each patient. RESULTS: 25 of 28 patients (89%) achieved 40 HU. The mean enhancement of empiric patients curves was 46.32 +/- 11.9 HU, the mean simulated enhancement was 46.62 +/- 4.3 HU S.D. (P= 0.48). 4.4 values per patient liver could be compared with the simulation curve (122 points for 28 patients): 50% of the patient curves were within a range of 5 HU compared with the simulation curve. CONCLUSION: Software simulation of contrast enhancement curves of the liver is a feasible and valuable method to predict individual liver enhancement curves. Improvements concerning the integration of cardiovascular parameters and preexisting liver parenchymal diseases into the simulation software have to be arranged.

Adult↗

PubMed1987

Age-related changes in social and psychological models predicting dental care in children.

Social and psychological factors associated with dental care were examined in two groups of children ages 6-8 and 9-11 years. Level of surface plaque, measures of dental health status (that is, total number of primary teeth decayed, missing, and filled [dmft] and total number of permanent teeth decayed, missing, and filled [DMFT] ), and frequency of dental visits were used as indicators of preventive behavior. The importance of social and psychological factors associated with these indicators was shown to vary with age group and with the specific preventive behavior indicator. Perceived level of dental anxiety and dental vulnerability were significantly associated with dental care, with dental anxiety being an important factor only in the lower group. Accessibility to a free school dental service was an important predictor of dental health status (DMFT) in the older age group, however, the data indicate that only when this service was offered within an organized structure of referral and transport was there an optimal effect on subsequent dental health.

Age Factors↗

PubMed1985

Comparison of reversed-phase columns for the separation of tryptic peptides by gradient elution. Correlation of experimental results and model prediction.

A total of 10 reversed-phase columns obtained from different suppliers were evaluated for their ability to separate typical peptide mixtures: tryptic digests of cytochrome c, lysozyme and collagen. Each column was tested in a standard gradient elution using phosphate buffer (pH 2.85) as the A-solvent and acetonitrile as the B-solvent. Some differences in band spacing for the various peptides were observed from column to column. More important differences were observed in the ability of these various columns to provide narrow peaks and good resolution, as measured by column peak capacity. These differences in column peak capacity were related to differences in column dimensions and particle size; it also appeared that C8 bonded phases were somewhat more efficient than were C18 phases. The recovery of cytochrome c digest from four of the columns was also assessed. Summed peak areas were proportional to sample size, as the latter was varied from 1 to 100 micrograms. The apparent recovery from each column did not vary by more than +/- 5%. From this it was concluded that these columns gave essentially quantitative recovery for this particular sample. Limited data on column life were obtained for some of these columns.

Animals↗

PubMed1983

Distribution of electrotonic synapses on identified lamprey neurons: a comparison of a model prediction with an electron microscopic analysis.

1. Intracellular recordings of the monosynaptic excitatory postsynaptic potential (EPSP) were made from an identified giant interneuron in the lamprey spinal cord following stimulation of a single identified presynaptic giant axon. The EPSP had both electrotonic and chemical components. 2. The giant interneuron and sometimes the giant axon were labeled with horseradish peroxidase (HRP). Using combined light and electron microscopy (EM), gap junctions formed by the axon on the HRP-labeled dendritic trees of seven interneurons were identified and their position marked on dendritic diagrams made from tracings of the cells. 3. The total number of gap junctions on a giant interneuron varied from a minimum of 9 to a maximum of 23. The number of gap junctions on a branch of a dendritic tree varied from 1 to 9. For all seven neurons the closest gap junction was located approximately 65 microns from the soma and the furthest 280 microns from the soma. 4. When gap junction position was plotted as a function of electrotonic distance from the soma, the variability in their distribution decreased significantly. Synaptic location was found to be on the average about 0.5 space constants from the soma, and this value compared favorably with that determined from an analysis of half-width and rise time of the electrotonic synaptic potential for these neurons. 5. These results suggest that the presynaptic axon tends to make, on the average, synaptic contact at the same electrical distance from the soma.

Animals↗

PubMed2003

Coronary calcium scoring: modelling, predicting and correcting for the effect of CT scanner spatial resolution on Agatston and volume scores.

The purpose of this study was to evaluate the impact of spatial resolution on coronary calcium scoring by x-ray CT, to assess the scoring performance of different CT scanners as they are operated in the field and to correct for the effects of CT scanner spatial resolution on coronary calcium scoring. A phantom consisting of five aluminium wires of known diameter in water was used to measure spatial resolution and to assess scoring performance. Fourteen CT scanners (three helical, two dual, two electron-beam and seven multi-detector) from four manufacturers were evaluated, some under different operating conditions. One scanner was monitored over a 3 month period and again 6 months later. Both spatial resolution and image pixel size significantly affect calcium scoring results. Spatial resolution can be measured with a precision of about 2%. Scanner spatial resolution ranged from 1 to 1.7 mm full-width-half-maximum (FWHM), and pixel size from 0.25 to 0.86 mm. Spatial resolution differences introduce systematic scoring differences that range from 38% to 1100% depending on wire size. Significant temporal variations in spatial resolution were observed in the monitored scanner. By correcting all the scanners to the same target spatial resolution, the standard deviation of individual scanners with respect to a mean value (the spread) can be reduced by 25-70% for different wires. In conclusion, scanner spatial resolution significantly affects calcium scoring and should be controlled for. Scanner performance can change over time. Under ideal conditions, CT scanners should be operated with a standard spatial resolution for calcium scoring. When this is not possible, post-processing correction is a viable alternative.

Arteriosclerosis↗

PubMed2004

G-CSF and IL-8 for early diagnosis of sepsis in neonates and critically ill children - safety and cost effectiveness of a new laboratory prediction model: study protocol of a randomized controlled trial [ISRCTN91123847].

INTRODUCTION: Bacterial infection represents a serious risk in neonates and critically ill paediatric patients. Current clinical practice is characterized by frequent antibiotic treatment despite low incidence of true infection. However, some patients escape early diagnosis and progress to septic shock. Many new markers, including cytokines, have been suggested to improve decision making, but the clinical efficacy of these techniques remains uncertain. Therefore, we will test the clinical efficacy of a previously validated diagnostic strategy to reduce antibiotic usage and nosocomial infection related morbidity. METHODS: All patients admitted to the multidisciplinary neonatal and paediatric intensive care unit of a university children's hospital will be included. Patients will be allocated either to routine sepsis work up or to the intervention strategy with additional cytokine measurements. Physicians will be requested to estimate the pre-test probability of sepsis and pneumonia at initial suspicion. In the treatment arm, physicians will receive raw cytokine results, the likelihood ratio and the updated post-test probability. A high post-test probability will suggest that immediate initiation of antibiotic treatment is appropriate, whereas a low post-test probability will be supportive of watchful waiting or discontinuing prophylactic empirical therapy. Physicians may overrule the suggestions resulting from the post-test probability. CONCLUSION: This trial will ascertain the clinical efficacy of introducing new diagnostic strategies consisting of pre-test probability estimate, novel laboratory markers, and computer-generated post-test probability in infectious disease work up in critically ill newborns and children.

Anti-Bacterial Agents↗

PubMed2006

SSR180711, a novel selective alpha7 nicotinic receptor partial agonist: (II) efficacy in experimental models predictive of activity against cognitive symptoms of schizophrenia.

SSR180711 (4-bromophenyl 1,4diazabicyclo(3.2.2) nonane-4-carboxylate, monohydrochloride) is a selective alpha7 nicotinic receptor (n-AChR) partial agonist. Based on the purported implication of this receptor in cognitive deficits associated with schizophrenia, the present study assessed efficacy of SSR180711 (i.p. and p.o.) in different types of learning and memory involved in this pathology. SSR180711 enhanced episodic memory in the object recognition task in rats and mice (MED: 0.3 mg/kg), an effect mediated by the alpha7 n-AChR, as it was no longer seen in mice lacking this receptor. Efficacy was retained after repeated treatment (eight administrations over 5 days, 1 mg/kg), indicating lack of tachyphylaxia. SSR180711 also reversed (MED: 0.3 mg/kg) MK-801-induced deficits in retention of episodic memory in rats (object recognition). The drug reversed (MED: 0.3 mg/kg) selective attention impaired by neonatal phencyclidine (PCP) treatment and restored MK-801- or PCP-induced memory deficits in the Morris or linear maze (MED: 1-3 mg/kg). In neurochemical and electrophysiological correlates of antipsychotic drug action, SSR180711 increased extracellular levels of dopamine in the prefrontal cortex (MED: 1 mg/kg) and enhanced (3 mg/kg) spontaneous firing of retrosplenial cortex neurons in rats. Selectivity of SSR180711 was confirmed as these effects were abolished by methyllycaconitine (3 mg/kg, i.p. and 1 mg/kg, i.v., respectively), a selective alpha7 n-AChR antagonist. Additional antidepressant-like properties of SSR180711 were demonstrated in the forced-swimming test in rats (MED: 1 mg/kg), the maternal separation-induced ultrasonic vocalization paradigm in rat pups (MED: 3 mg/kg) and the chronic mild stress procedure in mice (10 mg/kg o.d. for 3 weeks). Taken together, these findings characterize SSR180711 as a promising new agent for the treatment of cognitive symptoms of schizophrenia. The antidepressant-like properties of SSR180711 are of added interest, considering the high prevalence of depressive symptoms in schizophrenic patients.

Analysis of Variance↗