Contamination of organic nutrient sources with potentially toxic elements, antibiotics and pathogen microorganisms in relation to P fertilizer potential and treatment options for the production of sustainable fertilizers: A review.

Organic nutrient sources such as farmyard manure, sewage sludge, their biogas digestates or other animal by-products can be valuable fertilizers delivering organic matter to the soil. Currently, especially phosphorus (P) is in the focus of research since it is an essential plant nutrient with finite resources, estimated to last only for some more decades. Efficient utilization of organic P sources in agriculture will help to preserve P resources and thereby has the potential to close nutrient cycles and prevent unwanted P-losses to the environment, one of the major causes for eutrophication of water bodies. Unfortunately, organic P sources usually contain also various detrimental substances, such as potentially toxic elements or organic contaminants like pharmaceuticals as well as pathogenic microorganisms. Additionally, the utilization of some of these substrates such as sewage sludge or animal by-products is legally limited in agriculture because of the potential risk to contaminate sites with potentially toxic elements and organic contaminants. Thus, to close nutrient cycles it is important to develop solutions for the responsible use of organic nutrient sources. The aim of this review is to give an overview of the contamination of the most important organic nutrient sources with potentially toxic elements, antibiotics (as one important organic contaminant) and pathogenic microorganisms. Changes in manure and sewage sludge management as well as the increasing trend to use such substrates in biogas plants will be discussed with respect to potential risks posed to soils and water bodies. Some examples for abatement options by which contamination can be reduced to produce P fertilizers with high amounts of plant available P forms are presented.

Direct effects of morphine but not of fentanyl-type opioids on human 5-HT3A receptors in outside-out patch-clamp studies.

BACKGROUND: The alkaloid morphine is historically the oldest opiate, yet still today it has clinically important uses in analgesic therapies. The main analgesic effect of opioids, including synthetic opioids belonging to the family of 4-anilidopiperidines, is mediated via activation of opioid receptors spread throughout the peripheral and central nervous system. However, morphine acting as a 'dirty' drug also exhibits effects on other receptor systems, e.g., the serotonergic system and its 5-HT3 receptor. Therefore, this study focuses on the interaction of morphine and fentanyl-type opioids (alfentanil, remifentanil and sufentanil) with 5-HT3A receptors. METHODS: Excised outside-out patches from human embryonic kidney-293 cells, stably transfected with the human 5-HT3A receptor cDNA, were used to determine the opioid effects using the patch-clamp technique. RESULTS: Within clinical concentrations, the effects of morphine are concentration-dependent. Morphine reduced current amplitudes, as well as activation and decay time constants. These effects were not competitive. Contrary to these results, all fentanyl-type opioids only exerted effects far above their clinical concentration ranges. These effects were not homogenous but varying. CONCLUSIONS: Morphine is an opioid compound exhibiting special antagonistic interaction with 5-HT3A receptors. This interaction is not shared by the newer synthetic derivatives of the fentanyl-type opioids in the clinical relevant concentration range.

If only....: failed, missed and absent error recovery opportunities in medication errors.

BACKGROUND: Systematic analysis of error recovery can provide hospitals with important information to help them improve their ability to detect and correct errors. Because errors will always crop up and 100% safety can never be achieved, hospitals should be able to prevent patient harm by timely and effective error recovery. METHODS: In this study, failed, missed and absent recovery opportunities were identified in 52 medication errors which all resulted in severe patient harm or patient death. For all identified recovery opportunities, the underlying failure factors were identified and classified according to the Eindhoven classification model. Those failure factors represent negative influences on error recovery. RESULTS: The number of recovery opportunities per error ranged from 0 to 11; on average, 2.4 recovery opportunities were identified. Of 127 identified recovery opportunities, 94 (74%) were planned and 33 (26%) were unplanned or ad hoc. Most failure factors underlying the planned recovery opportunities were organisational failure factors; most failure factors underlying the unplanned recovery opportunities were human failure factors. CONCLUSIONS: From this study, it can be concluded that actual accidents can be used as an alternative data source to near misses for the analysis and understanding of error recovery. By using both sources, hospitals can enhance their resilience by reinforcing the positive influences on error recovery as well as reducing the negative ones. Together with traditional error reduction methodologies, which only concentrate on eliminating failure factors, hospitals thus have numerous opportunities to improve patient safety.

Feasibility and reliability of PRISMA-medical for specialty-based incident analysis.

AIMS AND OBJECTIVES: In this study, the feasibility and reliability of the Prevention Recovery Information System for Monitoring and Analysis (PRISMA)-Medical method for systematic, specialty-based analysis and classification of incidents in the neonatal intensive care unit (NICU) were determined. METHODS: After the introduction of a Neonatology System for Analysis and Feedback on Medical Events (NEOSAFE) in eight tertiary care NICUs and one paediatric surgical ICU, PRISMA-Medical was started to be used to identify root causes of voluntary reported incidents by multidisciplinary unit patient safety committees. Committee members were PRISMA-trained and familiar with the department and its processes. In this study, the results of PRISMA-analysis of incidents reported during the first year are described. At t = 3 months and t = 12 months after introduction, test cases were performed to measure agreement at three levels of root cause classification using PRISMA-Medical. Inter-rater reliability was determined by calculating generalised kappa values for each level of classification. RESULTS: During the study period, 981 out of 1786 eligible incidents (55%) were analysed for underlying root causes. In total, 2313 root causes were identified and classified, giving an average of 2.4 root causes for every incident. Although substantial agreement (kappa 0.70-0.81) was reached at the main level of root cause classification of the test cases (discrimination between technical, organisational and human failure) and agreement among the committees at the second level (discrimination between skill-based, rule-based and knowledge-based errors) was acceptable (kappa 0.53-0.59), discrimination between rule-based errors (the third level of classification) was more difficult to assess (kappa 0.40-0.47). CONCLUSION: With some restraints, PRISMA-Medical proves to be both feasible and acceptably reliable to identify and classify multiple causes of medical events in the NICU.

Integration of prospective and retrospective methods for risk analysis in hospitals.

OBJECTIVE: To explore how hospital management could gain a better picture of risks to support them in setting priorities for patient safety. METHODS: and SETTING: This study deals with the combined application of prospective and retrospective methods for risk analysis on two units of a Dutch general hospital. In the prospective analyses, employees identified and assessed possible risks in selected processes. In the retrospective analyses, incidents were reported by employees and subsequently investigated. The methods were integrated by using information from retrospective incident reports for prospective risk identification and assessment, and by matching their categorization schemes. Two evaluation forms provided insight into the perceived usefulness of the methods and their integration. RESULTS: and CONCLUSIONS: For both units, the prospective and retrospective analyses resulted in divergent overviews of risks in terms of nature and magnitude, which suggests that one or both methods were subject to biases. Findings from the evaluation forms showed that both methods were perceived as useful and that triangulation provided additional insight into risks. Due to the convergent evidence, triangulation of prospective and retrospective methods can provide hospital management and frontline staff with a more complete and less biased picture of risks. An integrative approach might be advantageous in terms of efficiency of analysis, setting priorities for patient safety and improving the methods themselves.

Integration of decentralized clinical data in a data warehouse: a service-oriented design and realization.

OBJECTIVES: In this paper we present a general concept and describe the difficulties for the integration of data from various clinical partners in one data warehouse using the Open European Nephrology Science Center (OpEN.SC) as an example. This includes a requirements analysis of the data integration process and also the design according to these requirements. METHODS: This conceptual approach based on the Rational Unified Process (RUP) and paradigm of Service-Oriented Architecture (SOA). RESULTS: Because we have to enhance the confidence of our partners in the OpEN.SC system and with this the willingness of them to participate, important requirements are controllability, transparency and security for all partners. Reusable and fine-grained components were found to be necessary when working with diverse data sources. With SOA the requested reusability is implemented easily. CONCLUSIONS: A key step in the development of a data integration process within such a health information system like OpEN.SC is to analyze the requirements. And to show that this is not only a theoretical work, we present a design - developed with RUP and SOA - which fulfills these requirements.

Prospective risk analysis of health care processes: a systematic evaluation of the use of HFMEA in Dutch health care.

The aim of this study was to evaluate the use of Healthcare Failure Mode and Effect Analysis (HFMEA) in Dutch health care by means of user feedback. Thirteen HFMEA analyses of various health care processes were successfully concluded and on average took 69 person-hours (excluding reporting). These results show that HFMEA can successfully be applied in Dutch health care. However, the user feedback also uncovered several perceived drawbacks, such as the fact that HFMEA is very time-consuming and that, particularly, the risk assessment part of HFMEA is difficult to carry out. Moreover, a lack of guidance with regard to the identification of failure mode causes and effective actions might influence the quality of the outcomes of an HFMEA analysis. Several suggestions are put forward to improve the perceived utility and acceptance of HFMEA. Nevertheless, future research is necessary to evaluate the actual effects of these recommendations. Error modelling and risk analysis, and their contribution to explaining human performance in socio-technical systems, traditionally belong to the field of ergonomics. The user feedback on HFMEA and the suggestions that are put forward may also be useful for (H)FMEA and hazard analysis and critical control point applications in sectors other than health care.

Tolerance of Japanese quail embryos and young chicks to hypothermia.

The purpose of this study was to explore the tolerance of Japanese quail (Coturnix coturnix japonica) embryos and young quail chicks to a very low ambient temperature. Fifty (n = 50) quail embryos at age embryonic age d 6 were placed in a cold room at 13 degrees C for 24 h. The heart rate (HR) was determined with an infrared HR sensor in an instrument called "Buddy." After 12 and 24 h, the average body temperature of the embryos was 13 degrees C with an average HR of 8.7 +/- 0.9 beats per minute (bpm). The average body temperature of 50 control embryos was 38 degrees C and they had an average HR of 301 +/- 15 bpm. The hypothermic quail embryos had a 24-h delay in hatching at 58% hatchability. The controls hatched on time at 81% hatchability. Twelve (n = 12) 6-d-old quail chicks were placed in a low-temperature environment (13 degrees C) for a period of 6 h. Quail from which the test group was selected were retained in a brooder to serve as the control comparison. The electrocardiogram HR for both hypothermic and control quail was recorded with a digital oscilloscope. The 12 quail in the low-temperature environment exhibited an immobile state of hypothermia. These hypothermic quail had an average HR of 7 +/- 0.6 bpm. The control quail had an average HR of 525 +/- 24 bpm. After emerging from the reduced-temperature environment, the immobile hypothermic quail were placed under an infrared light that produced a brooder-like temperature of 33 degrees C. After 40 min, all quail could walk around and some ate and drank.

Specialty-based, voluntary incident reporting in neonatal intensive care: description of 4846 incident reports.

OBJECTIVES: To examine the characteristics of incidents reported after introduction of a voluntary, non-punitive incident reporting system for neonatal intensive care units (NICUs) in the Netherlands; and to investigate which types of reported incident pose the highest risk to patients in the NICU. DESIGN: Prospective multicentre survey. METHODS: Voluntary, non-punitive incident reporting was introduced in eight level III NICUs and one paediatric surgical ICU. An incident was defined as any unintended event which (could have) reduced the safety margin for the patient. Multidisciplinary, unit-based patient safety committees systematically collected and analysed incident reports, and assigned risk scores to each reported incident. Data were centrally collected for specialty-based analysis. This paper describes the characteristics of incidents reported during the first year. Bivariate logistic regression analysis was conducted to identify high-risk incident categories. RESULTS: There were 5225 incident reports on 3859 admissions, of which 4846 were eligible for analysis. Incidents with medication were most frequently reported (27%), followed by laboratory (10%) and enteral nutrition (8%). Severe harm was described in seven incident reports, and moderate harm in 63 incident reports. Incidents involving mechanical ventilation and blood products were most likely to be assigned high-risk scores, followed by those involving parenteral nutrition, intravascular lines and medication dosing errors. CONCLUSIONS: Incidents occur much more frequently in Dutch NICUs than has been previously observed, and their impact on patient morbidity is considerable. Reported incidents concerning mechanical ventilation, blood products, intravascular lines, parenteral nutrition and medication dosing errors pose the highest risk to patients in the NICU.

The effects of morphine on human 5-HT3A receptors.

5-HT3 receptors are ligand-gated ion channels that are involved in the modulation of emesis and pain. In this study, we investigated whether the opioid analgesic, morphine, exerts specific effects on human 5-HT3 receptors. Whole-cell patches from HEK-293 cells stably transfected with the human 5-HT3A receptor cDNA were used to determine the effects of morphine on the 5-HT-induced currents using the patch clamp technique. At negative membrane potentials, 5-HT induced inward currents in a concentration-dependent manner. The 5-HT3 receptor antagonist, ondansetron, (0.3 nM) reversibly inhibited the 5-HT-induced signals. Morphine reversibly suppressed 5-HT-induced peak currents as a function of concentration (IC50 = 1.1 microM, Hill coefficient = 1.2). The block by morphine decreased with increasing 5-HT concentrations, suggesting a competitive effect. In addition, the activation, as well as the inactivation, kinetics of the currents were significantly slowed in the presence of morphine. The morphine antagonist, naloxone, also inhibited 5-HT-induced currents (e.g., at 3 microM by 17%). The effects of morphine and naloxone were not additive. The potency of morphine and the competitivity of the blocking effect points to a specific mechanism at a receptor site rather than an unspecific membrane effect.

Error recovery in a hospital pharmacy.

A field study was performed in a hospital pharmacy aimed at identifying positive and negative influences on the process of detection of and further recovery from initial errors or other failures, thus avoiding negative consequences. Confidential reports and follow-up interviews provided data on 31 near-miss incidents involving such recovery processes. Analysis revealed that organizational culture with regard to following procedures needed reinforcement, that some procedures could be improved, that building in extra checks was worthwhile and that supporting unplanned recovery was essential for problems not covered by procedures. Guidance is given on how performance in recovery could be measured. A case is made for supporting recovery as an addition to prevention-based safety methods.

Identification and classification of the causes of events in transfusion medicine.

BACKGROUND: Transfusion medicine lacks a standard method for the systematic collection and analysis of event reports. Review of event reports from the Food and Drug Administration (FDA) showed a relative paucity of information on event causation. Thus, a causal analysis method was developed as part of a prototype Medical Event Reporting System for Transfusion Medicine (MERS-TM). STUDY DESIGN AND METHODS: MERS-TM functions within existing quality assurance systems and utilizes descriptive coding and causal classification schemes. The descriptive classification system, based upon current FDA coding, was modified to meet participant needs. The Eindhoven Classification Model (Medical Version) was adopted for causal classification and analysis. Inter-rater reliability for the MERS-TM and among participating organizations was performed with the development group in the United States and with a safety science research group in the Netherlands. The MERS-TM was then tested with events reported by participants. RESULTS: Data from 503 event reports from two blood centers and two transfusion services are discussed. The data showed multiple causes for events and more latent causes than previously recognized. The distribution of causes was remarkably similar to that in an industrial setting outside of medicine that uses the same classification approach. There was a high degree of inter-rater reliability when the same events were analyzed by quality assurance personnel in different participating organizations. These personnel found the method practical and useful for providing new insights into conditions producing undesired events. CONCLUSION: A generally applicable and reliable method for identifying and quantifying problems that exist throughout transfusion medicine will be a valuable addition to event reporting activity. By using a common taxonomy, participants can compare their experience with that of others. If proven as readily implementable and useful as shown in initial studies, MERS-TM is a potential standard for transfusion medicine.

The attributes of medical event-reporting systems: experience with a prototype medical event-reporting system for transfusion medicine.

OBJECTIVE: To design, develop, and implement a prototype medical event-reporting system for use in transfusion medicine to improve transfusion safety by studying incidents and errors. METHODS: The IDEALS concept of design was used to identify specifications for the event-reporting system, and a Delphi and subsequent nominal group technique meetings were used to reach consensus on the development of the system. An interdisciplinary panel of experts from aviation safety, nuclear power, cognitive psychology, artificial intelligence, and education and representatives of major transfusion medicine organizations participated in the development process. Setting.- Three blood centers and three hospital transfusion services implemented the reporting system. RESULTS: A working prototype event-reporting system was recommended and implemented. The system has seven components: detection, selection, description, classification, computation, interpretation, and local evaluation. Its unique features include no-fault reporting initiated by the individual discovering the event, who submits a report that is investigated by local quality assurance personnel and forwarded to a nonregulatory central system for computation and interpretation. CONCLUSIONS: An event-reporting system incorporated into present quality assurance and risk management efforts can help organizations address system structural and procedural weakness where the potential for errors can adversely affect health care outcomes. Input from the end users of the system as well as from external experts should enable this reporting system to serve as a useful model for others who may develop event-reporting systems in other medical domains.

Amyotrophic lateral sclerosis of Guam: the nature of the neuropathological findings.

To elucidate the fundamental differences and similarities of the neuropathological features and etiopathogenesis of the amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) of Guam, we conducted a topographic, quantitative and histological investigation of tau-containing neurons, neurofibrillary tangles (NFTs), Bunina bodies and ubiquitinated inclusion bodies in 27 non-ALS non-PDC Guamanian subjects, as well as 10 Guam ALS patients, 28 PDC patients, and 5 patients with combined ALS and PDC (ALS-PDC). The topographic distribution of NFTs was basically the same in each disease and also in the non-ALS non-PDC group. There were relatively few, if any, NFTs in non-ALS non-PDC subjects and ALS patients, but there were many, especially in the frontal and temporal cortex, in Guam PDC and ALS-PDC patients. The histological and ultrastructural features of Bunina bodies in Guam ALS and ALS-PDC patients were similar to those reported in classic ALS. The ratio of occurrence of the inclusion in Guam ALS and ALS-PDC patients was similar to that reported so far in classic ALS. Ubiquitinated skein-like inclusion bodies were observed in the spinal anterior horn cells in Guam ALS and ALS-PDC patients. These findings indicate that classic ALS does exist on Guam, that NFTs in Guam ALS patients are merely a background feature widely dispersed in the population, that the mechanism of neuronal degeneration of Guam ALS is basically different from that of PDC, and that Guam ALS occurs initially are classic ALS.

Developing and using cognitive task typologies.

Based on experiences from case studies, some preliminary thoughts are presented regarding the why and how of developing a cognitive task typology model. Three different practical functions of such a typology are outlined: comparison, prediction, and design. These functions can be applied to sets of tasks both in the same and in different task worlds (e.g. artificial/laboratory tasks vs. real-life/case study tasks). Several existing techniques may be suitable for this purpose: hierarchical task analysis, verbal protocols, and the use of elementary cognitive modules. Finally two partly overlapping approaches to identify relevant task dimensions for a typology are outlined: one based on a macro-ergonomic view of human-machine systems, and the other centred around the cognitive concept of an operator's mental model of the task. In the Discussion a bottom-up strategy for typology development is advocated, and the relationship with task complexity is noted.

Fast regeneration of the olfactory nerve in goldfish: fine structure and behaviour.

Normal olfaction-guided behaviour in goldfish returns surprisingly fast after bilateral transection of the olfactory nerve (ON). In order to find correlation between morphological changes and behaviour we performed parallel studies on the behaviour of the fish and the ultrastructure of the olfactory bulb in axotomised fish. Signs of degeneration were most prominent between the 4th and 6th day post-operatively. First appearance of regenerated ON fibres and terminals was noted on the 10th post-operative day. ON terminals became frequent again two weeks after the operation. This supports earlier suppositions that morphological regeneration plays a crucial role in the fast and complete restoration of olfaction-guided behaviour.

Synthetic modification of a novel microbial ionophore: exploration of anticoccidial structure-activity relationships.

While fermentation-derived polyether ionophores such as salinomycin are the dominant class of anticoccidial feed additives, there is little information concerning the structural features which confer optimal potency/efficacy in this important series. The recently discovered microbial polyether 1a, featuring potent, broad-spectrum anticoccidial activity, was employed as a template to explore structure-activity relationships. A number of single-step synthetic modifications targeted structural changes in both the lipophilic carbon backbone and the ion-binding cavity of 1a. Although previous semisynthetic transformations among the polyether ionophores almost always resulted in a substantial loss of anticoccidial activity, we obtained several analogues, altered on the periphery of the ionophore-ion complex, which retain good potency and efficacy. Monoglycone 7 (semduramicin sodium) has the most impressive anticoccidial profile of this series, and is undergoing further biological testing under field conditions.

Auditory spatial alternation transforms auditory time.

Recent research has shown that a sequence of auditory events that is alternated between the ears is stretched out in auditory memory, as compared with nonalternating sequences. Although the stimulus-onset asynchronies (SOAs) of the interaural and monaural sequences were the same, the perceptual-onset asynchronies (POAs) differed by 24 msec. Because this result was only established for a restricted range of SOAs (125-250 msec), the present study tested a much larger range (40-2,130 msec). It turned out that the POA difference of 25 msec remained invariant over this whole range. Furthermore it was investigated how the angle of alternation affected the POA difference. It was found that (a) this difference increased linearly with increasing angular separation, and (b) the effects of SOA and angular separation on the POA difference were additive. The merits of six different attention-switching models were inspected to explain these results, but none of the models could describe the effects satisfactorily. We offer a new model, the space-time network, that copes not only with the present results but also explains several other studies reported in the literature.

Structure-activity studies of configurationally rigid arylprostaglandins.

Potent, albeit nonselective, smooth-muscle stimulant activity has been previously reported for 16-phenoxy- and 17-phenylprostaglandins, a finding that led to the design and development of the tissue-selective uterine stimulant sulprostone. As an extension of this work, analogues incorporating the 16-phenoxy and 17-phenyl substituents into the rigid indanyl, tetrahydronaphthyl, dihydrobenzofuryl, and dihydrobenzopyranyl ring systems were prepared and evaluated for uterine stimulant activity in vitro and diarrheal effects in vivo. Since these cyclic groups, with the exception of the indanyl, contain a chiral center, both optical antipodes were prepared. These studies demonstrate that ring size, heteroatom, and absolute configuration at C-16 are important determinants for potency and selectivity.