Expression of heat shock protein 70 in a permanent cell line (EPC) exposed to sediment extracts from the North Sea and the Baltic Sea.

Heat shock proteins 70 (hsp70) are known to be induced by a great variety of chemical stressors. The effects of different environmental contaminants, which were identified in sediments of the North Sea and the Baltic Sea as main contaminants or as contaminants of special toxicological interest, on the extent of expression of hsp70 in a permanent cell line Epithelioma papulosum cyprini (EPC) were investigated. Concentrations of the single contaminants leading to elevated hsp70 levels were compared to the respective concentrations of these contaminants encountered in the sediment extracts thus allowing an assessment of their contribution to the toxicity of these sediments. Analysis of hsp70 was performed using western blotting techniques with subsequent comparative quantification by densitometry. Eleven of thirteen contaminants have shown a dose-dependent increase in hsp70 levels. An expression of hsp70 was observed in most cases between 0.1 and 10 microg/mL test solution. Some of the investigated stressors led to extremely high hsp70 contents even at low concentrations. However, in most cases contaminant concentrations in sediments were too low to cause an effect. For this reason, effects of the tested sediments are attributed to other contaminants or rather to mixtures of stressors.

Unit-wide notification of ventilator disconnections.

The alarms generated by mechanical ventilators when patients become disconnected can blend in with other typical sounds of the intensive care unit. Ventilator alarms that go unnoticed for extended periods of time often result in permanent patient harm or death. We developed a unit-wide system to monitor ventilator disconnection alarms. When a disconnection is identified, the system takes control of every computer in the patient's intensive care unit and generates an enhanced audio and visual alert. This system was tested in four ICUs at LDS Hospital. Acceptance by medical personnel was very high and patient safety was improved through early intervention that avoided prolonged hypoxia. In addition, the system facilitated root cause analyses and new safety strategies.

The treatment of inflammatory arthritis with methotrexate in clinical practice: treatment duration and incidence of adverse drug reactions.

OBJECTIVE: To identify the proportion of patients with inflammatory arthritis who remain on methotrexate in the medium to long term and the incidence of side-effects in clinical practice. METHOD: The study population comprised all patients with inflammatory arthritis treated with methotrexate and monitored in clinics under the auspices of Staffordshire Rheumatology Centre. Two clinical auditors collected data retrospectively from the computer database used to support monitoring of patients on disease-modifying anti-rheumatic drugs. Information was collected on duration of treatments and reasons for stopping treatment. For patients identified as having potentially serious side-effects or who died whilst taking methotrexate, further information on their outcome was collected from patients' medical notes and where applicable post mortem reports and death registers. RESULTS: Between 1986 and 1999, 673 patients were treated with methotrexate, of whom 551 had a diagnosis of rheumatoid arthritis. From the Kaplan-Meier analysis, the probability of patients remaining on treatment 5 yr after starting methotrexate was 0.74. Three hundred and sixteen patients stopped methotrexate between 1986 and 1999. In 117 patients, the methotrexate was restarted. Seventy-two patients (10.7% of all patients) stopped because of inefficacy or patient choice or situation. Thirty-seven patients (5.5%) stopped methotrexate due to abnormal haematology (usually low neutrophils). Thirty-seven patients (5.5%) stopped methotrexate due to abnormalities in liver function tests. Life-threatening side-effects were identified in 12 patients (1.8%). These included six pneumonitis, five cytopenias and one disseminated varicella zoster. Two of these patients (0.3%) died, one from pneumonitis and one from disseminated varicella zoster. A total of 25 patients (3.7%) died while taking methotrexate and four died (0.6%) within 3 months of stopping methotrexate. One death (0.15%) was directly attributable to methotrexate (methotrexate pneumonitis). CONCLUSION: This study has shown that methotrexate is well tolerated in clinical practice in the medium to long term. It has produced accurate data on the incidence of adverse effects of methotrexate in a local population in a non-research setting. It has identified the incidence of life-threatening side-effects to be 1.7% with one death (0.15%) directly due to methotrexate. This information should prove useful when recommending such treatment to patients with inflammatory arthritis.

Amnesia and the declarative/nondeclarative distinction: a recurrent network model of classification, recognition, and repetition priming.

A key claim of current theoretical analyses of the memory impairments associated with amnesia is that certain distinct forms of learning and memory are spared. Supporting this claim, B. J. Knowlton and L. R. Squire found that amnesic patients and controls were indistinguishable in their ability to learn about and classify strings of letters generated from a finite-state grammar, but that the amnesics were impaired at recognizing the training strings. We show, first, that this pattern of results is predicted by a single-system connectionist model of artificial grammar learning (AGL) in which amnesia is simulated by a reduced learning rate. We then show in two experiments that a counterintuitive assumption of this model, that classification and recognition are functionally identical in AGL, is correct. In three further simulation studies, we demonstrate that the model also reproduces another type of dissociation, namely between recognition memory and repetition priming. We conclude that the performance of amnesic patients in memory tasks is better understood in terms of a nonselective, rather than a selective, memory deficit.

Evidence for the application of rules in Pavlovian electrodermal conditioning with humans.

Two Pavlovian SCR conditioning experiments investigated interference effects in sequential training of positive and negative patterning discriminations in humans. In Experiment 1, positive patterning (A-, B-, AB+) was trained in Phase 1, immediately followed by a negative patterning schedule (C+, D+, CD-). We predicted that human participants would learn a specific numerosity rule in positive patterning, which interferes with the subsequent negative patterning schedule. In Experiment 2, negative patterning (C+, D+, CD-) was trained in Phase 1, followed by a positive patterning schedule (A-, B-, AB+) in Phase 2. Because human participants would learn an abstract 'separate-versus-together'- or 'opposite'-rule to solve the negative patterning discrimination in Phase 1, there should be less interference in positive patterning in Phase 2 where the separate/together-rule could be applied, too. In both experiments, the initial patterning discriminations were acquired successfully. In Experiment 1, human participants totally failed to solve the Phase 2 discrimination, while in Experiment 2 appropriate response differentiation developed in Phase 2. Thus, without pre-experience human participants seem to utilize a specific numerosity-rule in positive patterning and a separate/together-rule in negative patterning.

Stimulus representations in human Pavlovian conditioning: implications of missing negative transfer across response systems.

Three Pavlovian conditioning experiments with human participants are reported, which investigated whether common or separate stimulus representations are involved in solving nonlinear discrimination tasks in different response systems. In our experiments we made use of a negative transfer effect between positive and negative patterning. Experiment 1 specified the conditions under which such a negative transfer effect occurs in human eyelid conditioning. Experiments 2 and 3 investigated whether a similar effect also occurs if two response systems--the eyelid and the skin conductance response system--are trained with trials of both types being randomly interleaved. The presence or absence of a negative transfer effect indicates whether or not the stimulus representations involved in the two conditioning processes overlap. The findings are discussed within the framework of a neuropsychological model of hippocampal function. The results suggest that the representations are distinct and thus support the idea of acquired equivalence and distinctiveness of stimulus representations.

The knowledge acquired during artificial grammar learning: testing the predictions of two connectionist models.

An artificial grammar learning experiment is reported which investigated whether three types of information are learned during this kind of task: information about the positions of single letters, about fragments of training strings, and about entire training strings. Results indicate that participants primarily learned information about string fragments and, to a lesser extent, information about positions of letters. Two connectionist models, an autoassociator and a simple recurrent network (SRN), were tested on their ability to account for these results. In the autoassociator simulations, similarity of test items to entire training items had a large effect, which was at variance with the experimental results. The results of the SRN simulations almost perfectly matched the experimental ones.

Learning artificial grammars: no evidence for the acquisition of rules.

Two experiments investigated whether there is evidence for acquisition of rules in implicit artificial grammar learning (AGL). Two different methods were used in meeting this goal, multiple regression analysis and analysis of receiver-operating characteristics (ROCs). By means of multiple regression analysis, several types of knowledge were identified that were used in judgments of grammaticality, for example, about single letters and about larger stimulus fragments. There was no evidence for the contribution of rule knowledge. The ROCs were in accord with a similarity-based account of AGL and thus did not support the notion that rule knowledge is acquired in AGL either. Simulations with a connectionist model corroborated the conclusion that the results were in accord with a similarity-based, associative account.

Evaluation of compliance with a computerized protocol: weaning from mechanical ventilator support using pressure support.

STUDY OBJECTIVES: To use a computerized consultation system to evaluate the feasibility of a mechanical ventilator weaning protocol which used the rapid shallow breathing index to guide adjustments in pressure support. A program to monitor user compliance and reasons for noncompliance was built into the computerized consultation system. METHODS: A total of nine critically ill patients (ten weaning episodes) were enrolled in the protocol. The respiratory therapists performed routine computer charting in the electronic database. They accepted or declined the explicit instructions generated by the computerized protocol and displayed on the bedside terminal. The consultation program monitored whether accepted instructions were implemented by the user. RESULTS: Patient's therapy was controlled by protocol for a total of 1075 h (mean 108 h, range 4 to 339 h) and 94.8% (1321/1394) of instructions were followed by the clinical staff. Of the 42 instructions clinical staff refused to follow, 23 (55%) were extubation instructions. There were 52 (3.7%) incorrect instructions generated with 24 software errors, 21 errors in underlying logic, and seven user misunderstanding errors. CONCLUSIONS: A high level of user compliance with this protocol was achieved. The methods described herein to monitor compliance and reasons for noncompliance within a protocol are reusable in the domain of mechanical ventilation and possibly in other domains.

Testing and validation of computerized decision support systems.

Systematic, through testing of decision support systems (DSSs) prior to release to general users is a critical aspect of high quality software design. Omission of this step may lead to the dangerous, and potentially fatal, condition of relying on a system with outputs of uncertain quality. Thorough testing requires a great deal of effort and is a difficult job because tools necessary to facilitate testing are not well developed. Testing is a job ill-suited to humans because it requires tireless attention to a large number of details. For these reasons, the majority of DSSs available are probably not well tested prior to release. We have successfully implemented a software design and testing plan which has helped us meet our goal of continuously improving the quality of our DSS software prior to release. While requiring large amounts of effort, we feel that the process of documenting and standardizing our testing methods are important steps toward meeting recognized national and international quality standards. Our testing methodology includes both functional and structural testing and requires input from all levels of development. Our system does not focus solely on meeting design requirements but also addresses the robustness of the system and the completeness of testing.

[Are there differences in processing times of variously complex rules in differential eyelid conditioning?]. / Unterscheiden sich die Verarbeitungszeiten unterschiedlich komplexer Regeln bei der differentiellen Konditionierung des Lidschlages?

Two logical relations, conjunction (AND) and exclusive disjunction (XOR) differ in formal complexity as well as in observable difficulties. AND results in less errors, fewer trials to criterion, and shorter processing time per trial than XOR. Two paradigms of differential classical conditioning are based on these rules. Negative patterning (A+, B+, AB-) equals XOR, and positive patterning (A-, B-, AB+) equals AND. We studied experimentally whether or not differences in processing time per trial are reflected in different optimal interstimulus intervals in human eyelid conditioning. Results of four groups (AND/XOR x 400/1200 ms; each group n = 10) suggest that differential conditioning could be observed in positive patterning (800-1000 ms) earlier than in negative patterning (1000-1200 ms).

Cost effective computerized decision support: tracking caregiver acceptance at the point of care.

We implemented a computerized decision support tool to standardize the administration of supplemental oxygen (O2) therapy in the acute care (non-ICU) hospital setting. Caregiver acceptance of the computerizeds oxygen therapy protocol (COTP) instructions was measured to determine the clinical performance of the computerized decision support tool. 49.6% of instructions generated were followed by the clinical caregiver, and 16.8% of instructions generated were explicitly acknowledged by the user through the COTP computer interface. Despite this low caregiver response rate, significant favorable changes in the administration of oxygen were observed. This paper is focused on the issues of general importance the caregiver response rate raises for the implementation and clinical use of computerized decision support tools, including: (1) limitations of the user interface and (2) inherent difficulty in changing long-standing practice patterns.

Clinical performance of a rule-based decision support system for mechanical ventilation of ARDS patients.

We developed a clinical decision support system--ventilation protocols--that managed tidal volume and ventilator rate settings during mechanical ventilation of patients with the Adult Respiratory Distress Syndrome (ARDS). We applied these protocols for a total of 10,903 hours in 40 ARDS patients. The clinical staff suspended the protocols for only 5% of the total application time due to medical procedures, surgeries, transient clinical problems not addressed by the protocols, or because of attending physician request. Of 3,148 instructions generated by the ventilation protocols, the clinical staff followed 2,932 (93%). The staff did not follow some instructions because of patient data errors, computer software and protocol logic errors, inability of the clinical staff to implement protocol instructions because of more pressing duties, and clinical staff objections to specific instructions. Sixty percent of the patients treated by the ventilation protocols survived. Our results demonstrate that the ventilation protocols provided a practical and safe decision support system for the mechanical ventilation of ARDS patients.

Salivary and serum antibodies in experimental canine taeniasis.

Specific IgG and IgA antibodies against adult Taenia pisiformis excretory/secretory antigen were detected in sera and saliva by enzyme-linked immunosorbent assay (ELISA) in experimentally infected dogs. IgG titres in serum and IgA in saliva corresponded with infection status, while serum IgA levels closely reflected faecal egg counts. The salivary IgA response was particularly raised and could have significant immunodiagnostic use for taeniasis in dogs.