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PubMed1997

Possibilities and limitations of magnetic source imaging of methohexital-induced epileptiform patterns in temporal lobe epilepsy patients.

The usefulness of MEG-based techniques in lateralizing and localizing the epileptogenic area was investigated in the present study. Spontaneous and methohexital-induced spikes were studied in a group of 15 patients with temporomesial epilepsy using a 37-channel neuromagnetometer. The accuracy of the magnetic source imaging was compared to the results of electrocorticographic (ECoG) recordings. Differences of drug-induced spike densities in the MEG recordings between both sides confirmed a similar lateralizing power of the MEG and ECoG recordings. Source location analyses based on a moving dipole model resp. a rotating dipole model were performed using a spherical head model. After subdivision of the volume of each patient's head, 8 cm3 cubicles containing at least 3 source locations were projected onto the individual MRI scan and resulted in source locations within or close to the presurgically defined primary epileptogenic area only in 3 of the 15 patients. Spike induction by methohexital has the advantage of shortening the recording period as compared to recordings of interictal epileptiform discharges. However, the correlation analyses of spike densities from MEG and ECoG recordings and the source location analyses from MEG recordings indicate that spike generated in deep temporomesial structures may escape the MEG registration.

Adolescent↗

PubMed2001

Strategic planning for ICCD clubhouse implementation: development of the Clubhouse Research and Evaluation Screening Survey (CRESS). International Center for Clubhouse Development.

The Clubhouse Research and Evaluation Screening Survey (CRESS) is a brief instrument designed to predict clubhouse readiness for certification assessment and, hence, performance in regard to expected model outcomes. The development of CRESS provides a practical example of the methodological challenges involved in creating a brief and valid screening instrument. Developed over a period of 5 years, CRESS is grounded in a series of workgroups, surveys, and pilot studies conducted by Fountain House and the International Center for Clubhouse Development (ICCD) in New York City. CRESS is shown to have criterion-oriented validity for the measurement of ICCD clubhouse model-related performance, as well as demonstrated ease in administration to a national sample of mental health programs.

Certification↗

PubMed1998

Interactions between P-glycoprotein substrates and other cationic drugs at the hepatic excretory level.

1. In the present study it was tested whether known P-glycoprotein (P-gp) substrates/MDR reversal agents interact with small (type 1) and bulky (type 2) cationic drugs at the level of biliary excretion in the rat isolated perfused liver model (IPRL). The studies were performed with model compounds tri-n-butylmethylammonium (TBuMA) (a relatively small type 1 organic cation), rocuronium (Roc) (a bulky type 2 organic cation) and the classical P-gp substrate doxorubicin (Dox). 2. Inhibitors were given in a 4 fold molar excess to the substrate studied. To minimize an interaction of the substrates at the hepatic uptake level, the competing compounds were added when over 55% to 85% of the administered dose of the model compounds had been removed from the perfusate and taken up by the liver. 3. We found a mutual interaction between TBuMA and procainamidethobromide (PAEB), both type 1 cationic compounds during biliary excretion. Interestingly, type 2 compounds, such as rocuronium, clearly inhibited type 1 cationic drugs as well as Dox secretion into bile, whereas type 1 compounds did not significantly inhibit type 2 drug excretion into bile. The type 1 cations PAEB and TBuMA only moderately inhibited Dox biliary excretion. Dox did not inhibit the biliary excretion of the type 2 agent rocuronium whereas rocuronium reduced Dox biliary excretion by 50% compared to controls. 4. MDR substrates/reversal agents like verapamil, quinine, quinidine and vinblastine strongly reduced both type 1 and type 2 organic cation excretion into bile. Dox secretion into bile was also profoundly reduced by these drugs, vinblastine being the most potent inhibitor in general. 5. The lack of mutual inhibition observed in some combinations of substrates may indicate that major differences in affinity of the substrates for a single excretory system exist. Alternatively, multiple organic cation transport systems with separate substrate specificities may be involved in the biliary excretion of amphiphilic drugs. Furthermore, the present study revealed a clear positive correlation between the lipophilicity of the potential inhibitors studied and their respective inhibitory activity on the biliary excretion of the model drugs investigated. 6. Our data are compatible with a potential involvement of P-glycoprotein in the hepatobiliary excretion of doxorubicin as well as of some type 1 and type 2 organic cations. Furthermore we postulate that the hydrophobic properties of the amphiphilic cationic drugs studied play a crucial role in the accommodation of these agents by P-glycoprotein and/or other potential cationic drug carrier proteins in the canalicular membrane.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Decomposing retrieval and integration in memory for actions: a multinomial modeling approach.

Typically, action phrases are recalled better if participants are asked to enact the phrases than if they are just asked to remember them. When investigating which processes constitute this enactment effect a difficulty is that observable effects in standard memory tests are ambiguous because such tests require several processes. In the present article, we introduce a multinomial model that decomposes observable memory performance into a retrieval parameter and a parameter concerning the item-specific processing and integration of an action phrase. These parameters are estimated from free recall and cued recall performance. The model fitted the data of two experiments designed to test it. Experiment 1 demonstrated the basic usefulness of the model by showing expected differences in the integration parameter in the absence of unexpected differences in the retrieval parameter. Experiment 2 extended the conditions under which the model is useful by showing expected differences in the retrieval parameter even in the presence of unexpected differences in the integration parameter. Together, these findings support our theoretical framework according to which enactment generally boosts integration of action phrases, but increases retrieval only for phrases with context cues.

Adult↗

PubMed2001

The pharmacokinetics of epidural ropivacaine in infants and young children.

UNLABELLED: The pharmacokinetic variables of ropivacaine were characterized after epidural bolus injection in pediatric patients. The subjects, 7 infants (aged 3-11 mo) and 11 young children (aged 12-48 mo), received 1.7 mg/kg of ropivacaine via a lumbar epidural catheter. Total plasma concentrations of ropivacaine measured over 24 h were assayed by high-pressure liquid chromatography, and pharmacokinetic modeling was performed by Nonlinear Mixed Effects Modeling analysis. The median peak venous plasma concentrations (C(max)) in infants and young children were 610 microg/L (interquartile range [IQR], 550-725 microg/L) and 640 microg/L (IQR, 540-750 microg/L), respectively. The median times to maximum plasma ropivacaine concentration (T(max)) were 60 min (IQR, 60-120 min) in infants and 60 min (IQR, 30-90 min) in young children. There were no statistical differences between median values of C(max) and T(max) between infants and young children. The calculated clearance (CL) in infants was 4.26 mL x min(-1) x kg(-1) (9% coefficient of variation), and in young children it was 6.15 mL x min(-1) x kg(-1) (11% coefficient of variation). The CL for infants was significantly less than the CL for young children (P < 0.01). The volume of distribution was estimated to be 2370 mL/kg (9% coefficient of variation) for both young children and infants. No systemic toxicity was observed in either group. IMPLICATIONS: This study revealed that the pharmacokinetic variables of lumbar epidural bolus ropivacaine in pediatric patients aged 3 to 48 mo are similar to those of adults, except that drug clearance was less in infants compared with older children.

Algorithms↗

PubMed1976

The performance of merging hospitals.

The primary aim of this paper is to examine the impact of mergers on the performance of hospitals. The study tests the null hypothesis that no significant differences exist in efficiency and effectiveness between hospitals that merge and those which remain independent entities. The performance evaluation model follows closely similar models used to study the performance of merging banks. The findings of the study suggest that 1) large urban hospitals contemplating merger should view carefully the trade-offs involved between efficiency and effectiveness as indicated by the measures employed in this study, since the evidence indicates that the increased service capability achieved in merging hospitals is accompanied by a significant increase in costs; and 2) the concept appears very promising for small rural hospitals, especially in veiw of evidence that various benefits extend over the short-, intermediate-, and long-range time frames employed in the study.

Costs and Cost Analysis↗

PubMed2000

Evaluating the simplified Conjoint Expected Risk model: comparing the use of objective and subjective information

The simplified Conjoint Expected Risk (CER) model by Holtgrave and Weber posits that perceived risk is a linear combination of the subjective judgments of the probabilities of harm, benefit, and status quo, and the expected harm and benefit of an activity. It modifies Luce and Weber's original CER model--that uses objective information to evaluate financial gambles--to accommodate activities such as health/technology activities where values of the model variables are subjective. If the simplified model is a valid modification of the original model, its performance should not be sensitive to the use of subjective information. However, because people may evaluate information differently when objective information is provided to them than when they generate information on their own, the performance of the simplified CER model may not be robust to the source of model-variable information. We compared the use of objective and subjective information, and results indicate that the estimates of the simplified CER model parameters and the proportion of variance in risk judgments accounted for by the model are similar under these two conditions. Thus, the simplified CER model is viable with activities for which harm and benefit information is subjective.

Journal Article↗

PubMed1991

Detection of silent temporal gaps in sinusoidal markers.

Gap detection thresholds were measured by forced-choice procedure for conditions where the duration of a silent gap was varied adaptively between pairs of sinusoidal markers of the same or different frequency. Frequencies of the first sinusoid in a pair of markers ranged from F1 = 500 to 4000 Hz. Second-sinusoid marker frequencies F2 included F1 = F2, and usually frequencies 2%, 5%, 24%, and 50% higher than F1. In preliminary studies the role of presentation level (E/N0) on gap detection was considered. Preliminary data revealed confounding extraneous factors arising from gating transients and from overall stimulus (i.e., markers + gap) and/or masker duration cues. In the main experiments, the contributions of these extraneous cues were evaluated with experimental designs aimed at identifying and minimizing the confounding roles of these cues in gap detection. For conditions where extraneous gating transient cues were minimized (by presenting the sinusoidal markers in a continuous noise masker with random onset phase for the second sinusoid in every pair of markers) and overall stimulus duration cues were diminished (by randomizing the duration of each marker independently), gap detection thresholds increased from 5 to 90 ms as the frequency separation between F1 and F2 was increased by half an octave. When the gap detection thresholds were treated as filter attenuation values by normalizing and converting the data into decibels, the data were closely fit by the roex filter model. On average, the listeners' performances were modeled well by a constant-percentage (7%) bandwidth filter centered on F1.

Attention↗

PubMed1997

Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection.

Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.

AIDS Vaccines↗

PubMed2002

Predicting the use of outpatient mental health services: do modeling approaches make a difference?

Studies attempting to project the impact of providing health coverage to the uninsured population have demonstrated considerable variation in the estimated costs of mental health care. Different modeling approaches to project health care use and costs have been shown to address some data characteristics well, but not all of them. Using data from Health Care for Communities, a recent national household survey, this paper attempts to estimate and predict the use of mental health outpatient services if insurance coverage were extended to the uninsured. The study employs two-part models, with the second part based on an ordinary least squares (OLS) approach and a generalized linear model (GLM), and a zero-inflated negative binomial model (ZINB). Estimates and predictions are not sensitive to the modeling approaches chosen, although the ZINB model out performs the two-part models in terms of out-of-sample prediction.

Community Mental Health Services↗

PubMed2002

Predicting levels of stress from biological assessment data: empirical models from the Eastern Corn Belt Plains, Ohio, USA.

Interest is increasing in using biological community data to provide information on the specific types of anthropogenic influences impacting streams. We built empirical models that predict the level of six different types of stress with fish and benthic macroinvertebrate data as explanatory variables. Significant models were found for six stressor factors: stream corridor structure; siltation; total suspended solids (TSS), biochemical oxygen demand (BOD), and iron (Fe); chemical oxygen demand (COD) and BOD; zinc (Zn) and lead (Pb); and nitrate and nitrite (NOx) and phosphorus (P). Model R2 values were lowest for the siltation factor and highest for TSS, BOD, and Fe. Model R2 values increased when spatial relationships were incorporated into the model. The models generally performed well when applied to a random subset of the data. Performance was more mixed when models were applied to data collected from a previous time period, perhaps because of a change in the spatial structure of these systems. These models may provide a useful indication of the levels of different stresses impacting stream reaches in the Eastern Corn Belt Plains ecoregion of Ohio, USA. More generally, the models provide additional evidence that biological communities can serve as useful indicators of the types of anthropogenic stress impacting aquatic systems.

Animals↗

PubMed2003

Training fourth-year medical students in critical invasive skills improves subsequent patient safety.

Complications after procedures performed by residents are thought to occur most often early in the first postgraduate year (PGY-1). We evaluated the number of pneumothoraces (PTXs) caused by central venous line insertion (CVLI) by two groups of PGY-1 residents in both the first 3 months of residency and the entire year from 1996 through 2000 to determine the impact of CVLI training on PTX. From 1996 through 1998 fourth-year medical students had no specific training in CVLI and learned on the job as residents. Starting with the Class of 1999 we replaced this approach with a structured program in CVLI. Didactic sessions detailing anatomy and technique were followed by skill performance in a fresh cadaver model. Students performed skills initially under the direct supervision of a faculty member, who provided immediate feedback. Videotapes of this performance were reviewed with the students by both surgeons and kinesiologists to correct deficits before repeat sessions. Skills were repeated until competence was attained. Graduating students have made up greater than 90 per cent of our two hospitals' PGY-1 residents since 1996. Because these residents are responsible for CVLI we are able to obtain performance follow-up in actual clinical settings. We obtained the number of PTXs caused by CVLI for the years 1996 through 2000 as well as for the first 3 months of each academic year (July through September) to determine the impact of our program on this serious complication. The number of PTXs during the first 3 months of 1996-1998 remained stable. After the introduction of our teaching program the number decreased significantly in the years 1999-2000 when compared with 1996-1998 (P = 0.004, t test). The overall yearly decrease for 1999 versus 1996-1998 approached significance (P = 0.06). The introduction of a structured teaching program of CVLI skills appears to have a positive impact in reducing morbidity of PTX. The greatest impact occurs within the first 3 months of the new PGY-1 academic year.

Catheterization, Central Venous↗

PubMed1994

[Rescue effect of 15-deoxyspergualin for acute rejection on heart transplantation--using a rat model].

15-Deoxyspergualin (DSG) attracts a lot of attention as an immunosuppressive drug which has less side effects these days. In the present study, we researched the rescue effect of DSG for acute rejection on heart transplantation (HTX) by using rat models. We performed 40 heterotopic heart transplantation models. We injected them DSG (group A: 5 mg/kg/day, group B: 10 mg/kg/day) intravenously through 3 days, starting from the 3rd day the 4th day, and the 5th day after HTX. Our previous study showed the pathology on the 3rd day after HTX corresponded to mild rejection, the 4th day to moderate rejection, and the 5th day to severe rejection. One day after the injection was completed, the recipients were sacrificed. The rescue effect was histopathologically assessed by H-E stain, and the action mechanism of DSG was considered by immunohistochemical stain using monoclonal antibodies, which were against CD4 positive cells, CD8 positive cells, and macrophages. In result, the rescue effect of DSG was significant in all groups, in comparison with controls, which had no immunosuppression. And the rescue effect of group B was superior to group A. We also found using a immunohistochemical technique, that DSG inhibited the accumulation of CD4 and CD8 positive cells. We concluded the rescue effect of DSG for acute rejection on HTX was significant, especially in 10 mg/kg/day even in the severe rejection. And the suppression of helper and cytotoxic T cells accumulation might be one of the action mechanisms of DSG.

Acute Disease↗

PubMed2003

Weight-elimination neural networks applied to coronary surgery mortality prediction.

The objective was to assess the effectiveness of the weight-elimination cost function in improving classification performance of artificial neural networks (ANNs) and to observe how changing the a priori distribution of the training set affects network performance. Backpropagation feedforward ANNs with and without weight-elimination estimated mortality for coronary artery surgery patients. The ANNs were trained and tested on cases with 32 input variables describing the patient's medical history; the output variable was in-hospital mortality (mortality rates: training 3.7%, test 3.8%). Artificial training sets with mortality rates of 20%, 50%, and 80% were created to observe the impact of training with a higher-than-normal prevalence. When the results were averaged, weight-elimination networks achieved higher sensitivity rates than those without weight-elimination. Networks trained on higher-than-normal prevalence achieved higher sensitivity rates at the cost of lower specificity and correct classification. The weight-elimination cost function can improve the classification performance when the network is trained with a higher-than-normal prevalence. A network trained with a moderately high artificial mortality rate (artificial mortality rate of 20%) can improve the sensitivity of the model without significantly affecting other aspects of the model's performance. The ANN mortality model achieved comparable performance as additive and statistical models for coronary surgery mortality estimation in the literature.

Adult↗

PubMed2002

On the use of genetic algorithms for response surface modeling in high-performance liquid chromatography and their combination with the Microsoft Solver.

Four genetic algorithms--the classical, Haupt's, Brunetti's and a modification of the classical algorithm suggested in the present paper--are examined when they are used for the modeling of response surfaces in high-performance liquid chromatography (HPLC). We found that the best results are obtained from our modification and the worst by Haupt's algorithm. The classical genetic algorithm gives satisfactory results, better than those of Brunetti's algorithm. We also ascertained that all genetic algorithms may get stuck in a local minimum other than the global one, except for our modification, which can be considered to approach a global method. Finally, the time needed for the optimization of a genetic algorithm and the combination of a genetic algorithm with a non-linear least-squares routine are considered and discussed.

Algorithms↗

PubMed1982

Instructional design for aircrew judgment training.

Aircrew training design has made significant progress during recent years. However, significant gaps exist both in design methodology and in existing skills. Training in decision-making and judgment is currently haphazard at best. After a brief review of recent literature, this paper presents a conceptual model of judgment performance. The theoretical model is an extrapolation from Jensen and unites the variables of cognitive complexity, time availability, uncertainty, and stress into one coherent model. The model is used to examine current aircrew training and to develop new training strategies for improving judgment performance.

Aerospace Medicine↗

PubMed1986

A model to describe social performance levels in elderly people.

In elderly patients illness clearly affects both their social activity and their ability to care for themselves. It is important in general practice to recognize this effect when managing old people with acute and chronic illness. A model is described which aims to facilitate estimations of social performance at various levels. By carrying out this estimation the type of ;social' help needed can be better assessed. The model's usefulness in anticipatory care is also described.

Activities of Daily Living↗

PubMed1998

The effect of alpha 1 adrenoceptor antagonist prazosin on capillary supply, blood flow and performance in a rat model of chronic muscle ischaemia.

OBJECTIVE: This study explores whether the a1 blocker prazosin improves capillarisation, blood flow and muscle performance in chronically ischaemic muscles. DESIGN: Rat skeletal muscles were made ischaemic by unilateral ligation of the common iliac artery. The animals received prazosin and muscle blood flow, performance and capillary supply were studied 2 or 5 weeks later. MATERIALS AND METHODS: Prazosin (50 mg/l) was given in drinking water to animals with limited or intact blood supply. Muscle isometric twitch tension and fatigue index and blood flow at rest and during contractions (estimated by radio labelled microspheres) were measured in tibialis anterior, TA, and extensor digitorum longus, EDL. Capillary supply (capillary/fibre ratio, C/F) was estimated in frozen muscle sections stained for alkaline phosphatase in TA, EDL and soleus, S. RESULTS: Prazosin increased significantly capillary supply in ischaemic muscles after 2 and 5 weeks and blood flow during contractions (control muscles 163 +/- 6 ml. 100 g-1 min-1; ligated 2 weeks 25 +/- 7, ligated +prazosin 116 +/- 38 ; ligated 5 weeks 27 +/- 7, +prazosin 137 +/- 29, p < 0.05 vs. ligated). Fatigue index (final/peak tension over 5 min contractions at 4 Hz in %) was significantly improved by prazosin after 2 weeks (FI = 69 +/- 3% controls, 35 +/- 4% ligation, 60 +/- 3% ligation +prazosin) and less after 5 weeks (52 +/- 12% ligation, 61 +/- 3% ligation +prazosin). In contrast, prazosin had no effect on muscle performance in normal muscles in spite of it increased C/F and blood flow. CONCLUSIONS: Alpha1 adrenoceptor blockade is an effective way for improvement of capillary supply, blood flow and muscle performance in ischaemic muscles; the effect on muscle performance is most pronounced 2 weeks after induction of ischaemia.

Adrenergic alpha-Antagonists↗