Methods permitting to test the influence of the matrix as well as of its local and temporal distribution on the plasma conditions in laser ablation-inductively coupled plasma mass spectrometry ...(LA-ICP-MS) are developed. For this purpose, the MS interface is used as plasma probe allowing to investigate the average plasma condition within the ICP zone observed in terms of temporal and spatial distribution of the matrix.
Inserted matrix particles, particularly when being atomized and ionized, can cause considerable changes in both electron density and plasma temperature thus influencing the ionization equilibrium of the individual analytes. In this context, the plasma probe covers a region of the plasma for which no local thermodynamic equilibrium can be assumed. The differences in temperature, identified within the region of the plasma observed, amounted up to 3000
K. While in the central region conditions were detected that would not allow efficient atomization and ionization of the matrix, these conditions improve considerably towards the margin of the area observed. Depending on the nature as well as on the temporally and locally variable density of the matrix, this can lead to varying intensity ratios of the analytes and explain fractionation effects. By means of a derived equation it is shown that the deviation of the intensity ratio from the concentration ratio turns out to be more serious the higher the difference of the ionization potential of the analytes observed, the lower the plasma temperature and the higher the matrix concentration within the area observed.
Signal equations basing on dispersion functions describing the measured temporal intensity distribution for laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS) used in scanning ...and drilling mode are developed. Variable ablation rates due to either varying focussing conditions typical for drilling mode and due to the changes of physical and chemical properties in inhomogeneous samples as typically investigated in scanning mode are considered for. The model accounts for intermixing of the sample aerosol within the sampling chamber, the influence of transport in a cylindrical transport channel and the fact that normally not the entire vapour generated and transported to the ICP can be observed. The absolute signal response is influenced by the actually ablated, transported and observed analyte mass. The dispersion functions describing the relative signal response depend on sample chamber volume, the volume of the transport channel, the laser shot frequency, the carrier gas flow rate and the part of observable cross-section at the MS interface compared to the entire cross-section filled by the vapour. All these parameters depend on the experimental set-up and the selected operating conditions only. Using the signal equation the influence of all mentioned parameters on signal course is shown both theoretically and experimentally. The signal equation can be used for calculation of optimal experimental conditions.
On this basis, an algorithm is proposed providing the relative temporal distribution of any analyte with significantly higher temporal resolution than the measured temporal intensity distribution itself. Furthermore, usage of dispersion functions for investigation of a given transport system, for explanation of typical signal deviations, for the proof of homogeneous regions in a heterogeneous sample, for examination of changes in ablation rate and for investigation of fractionation effects is shown.
A transport model is proposed that describes the temporal intensity distribution observed in laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) in single-shot mode using ...quantitative signal equations. Calculations aim on the deduction of the dispersion function describing the time-dependent part of the signal equation.
The dispersion function depends on transport time in the centre of the transport tube, as related to carrier gas flow rate and tube volume and on the relation between carrier gas flow rate and ablation chamber volume. The equations describing the signal shape standardize signals from different systems and allow quantitative optimization of the ablation chamber, the transport tube and the detector.
Application of the model to ICP-MS shows that only a part of the area filled by the transported vaporization product and thus only a part of the transported vaporization product can be observed at the detector. The model is able to quantify both fractions.
As was calculated, the observed fraction of analyte is always higher than the observed fraction of the sample containing cross section and depends on the chosen transport parameters characterising the dispersion function. Thus, the determination of the signal integrals in the usual way can lead to systematic errors if the parameters influencing the dispersion function are variable.
Therefore, a different method of analysis based on signal equations is proposed and demonstrated. By this method of data treatment, all important system parameters influencing the dispersion function could be calculated and matched with theoretical ones. Furthermore, a complete integral of the transient signal including its statistical variation can be generated from a limited number of measurement points. For example, this can be applied to signals detected incompletely because of detector saturation and enables the use of high-abundance elements as internal standards.
Furthermore, the method can be used to monitor system performance, to identify the flow regime inside the ablation chamber, to take into account the sample volume for quantitative analysis and finally, to detect anomalous signal distributions that would lead to systematic errors. The prospects and limitations of the model are discussed for LA-ICP-MS in single shot mode.
Purpose: There is an increasing emphasis on quality indicators for documenting the performance of clinical radiotherapy equipment and processes. Such indicators, if relevant and unambiguous, can ...facilitate both external peer review audit (AAMP's‐ TG103) and internal review as a component of a quality improvement program. We present, for discussion, a graduated structural quality indicator to assess QC protocol compliance with existing performance standards and illustrate its use for linear accelerators and CT‐simulators. Method and Materials: Our structural quality indicator is based on four features of the equipment QC protocol; tolerance level, action level, frequency and documentation of each test. The structural quality indicator is divided into five levels of compliance: full, substantial, partial, minimal, and non compliance. Each individual test in a local QC protocol can be assigned to one of the five categories using the proposed indicator. To evaluate the indicator for relevance, absence of ambiguity and ease of use, it was used to check the compliance of local Tom Baker Cancer Centre QC procedures (daily, monthly, and annually) against Canadian standards (www.medphys.ca) and the AAPM's‐TG40 and TG66. Results: The results show that our Linac QC protocols were 82% and 88% in full or substantial compliance with CAPCA and AAPM's‐TG40 respectively. However, in the case of the CT‐simulator, full compliance was only 42% for CAPCA and 65% for AAPM's TG66. The form of the indicator facilitates the accurate identification of the discrepancies between the local protocol and the standard and hence guides remedial measures where necessary. Conclusion: A simple structural quality indicator for the evaluation of the documentary basis of a quality control program has been developed and applied. It is easy to use, relatively unambiguous and could form an objective component of a peer review exercise or a formal quality improvement program.
Purpose: To compare experience with a comprehensive incident learning system implemented in two radiation treatment programs and assess utility in reducing the probability of repeat adverse ...occurrences and improving patient safety. Method and Materials: An incident learning system specifically tailored to a radiation therapy program and based on published principles was implemented in two large academic cancer centers. In the adopted system, every incident, whether or not there is a resulting direct impact on patient treatments, is recorded, investigated to determine basic causes and strategies developed to correct system weaknesses. The two centers are closely matched in size with both centers being tertiary comprehensive clinical and academic centers and both having the same number of treatment units. Incidents are categorized into one of 5 types: clinical, operational, occupational, environmental and security/other. Four levels of severity are defined — critical, major, serious and minor. Results: Our analysis is based on 392 and 658 incidents reported by Centers A and B respectively. The majority of incidents in both centers were classified as clinical as distinct from operational or other categories. Both centers reported more clinical incidents during the treatment planning process than in other work domains. The distribution of incident severity shows remarkable agreement between the centers with 92% of all incidents at both centers classified as minor. Additionally, the distribution of the primary basic causes assigned to each incident also shows similarities between the two centers with 52% and 82% of the incidents reported at Centers A and B respectively assigned the same basic cause, i.e., that standards, procedures or practices were not followed, developed or adequately communicated. Conclusions: Our results indicate that an effective incident learning system implementation will strongly encourage the reporting of potential incidents as a proactive means of enhancing safety and quality.
In 105 consecutive patients with de novo acute myeloid leukemia (French-American-British M3 excluded), we compared prospectively the risk of bleeding complications, the number of platelet and red ...blood cell transfusions administered, and the costs of transfusions using two different prophylactic platelet transfusion protocols. Two hundred sixteen cycles of induction or consolidation chemotherapy and 3,843 days of thrombocytopenia less than 25 x 10(9)/L were evaluated. At the start of the study, each of the 17 participating centers decided whether they would use a 10 x 10(9)/L prophylactic platelet transfusion trigger (group A/8 centers) or a 20 x 10(9)/L trigger (group B/9 centers). Bleeding complications (World Health Organization grade 2-4) during treatment cycles were comparable in the two groups: 20 of 110 (18%) in group A and 18 of 106 (17%) in group B (P = .8). Serious bleeding events (grade 3-4) were generally not related to the patient's platelet count but were the consequence of local lesions and plasma coagulation factor deficiencies due to sepsis. Eighty-six percent of the serious bleeding episodes occurred during induction chemotherapy. No patient died of a bleeding complication. There were no significant differences in the number of red blood cell transfusions administered between the two groups, but there were significant differences in the number of platelet transfusions administered per treatment cycle: pooled random donor platelet concentrates averaged 15.4 versus 25.4 (P < .01) and apheresis platelets averaged 3.0 versus 4.8 (P < .05) for group A versus group B, respectively. This resulted in the cost of platelet therapy being one third lower in group A compared with group B without any associated increase in bleeding risk.
Both, droperidol and the new 5-HT3-antagonist (e.g. dolasetron) are effective drugs in the prevention of postoperative nausea and vomiting (PONV). It was the aim of this prospective double blind ...placebo controlled study to determine the efficacy of low-dose droperidol, dolasetron, and a combination of both drugs in the prevention of PONV after extracapsular cataract extraction.
148 inpatients undergoing cataract surgery were stratified according to gender and then randomised to receive one of four antiemetic regimens: placebo, droperiodol (10 micrograms x kg-1), dolasetron (12.5 mg), or the combination of both drugs (10 micrograms x kg-1 + 12.5 mg). The drugs were administered intravenously 5-10 minutes before the end of anaesthesia. General anaesthesia and the perioperative management of the patients were standardised: benzodiazepine premedication, induction with etomidate, alfentanil and mivacurium. Maintenance using desflurane in N2O/O2, and a continuous infusion of mivacurium was used. Postoperative analgesia (diclofenac or paracetamol) and antiemetic rescue medication (dimenhydrinate and metoclopramide) was standardised. Nausea, episodes of vomiting, retching and the need for additional antiemetics were recorded for 24-hours. The severity of PONV was categorised using a standardised scoring algorithm. The main aim of the study was the number of patients who stayed completely free from PONV.
There were no differences between the two groups with regard to biometric data, type of surgery, and distribution of risk factors for developing PONV. In all three treatment groups significantly less patients suffered from PONV (placebo: 66%; droperidol: 89%, dolasetron: 92%, combination: 89%; p = 0.011). Furthermore, the severity of PONV was reduced (p = 0.012).
Low-dose droperidol and dolasetron are equally effective to reduce the incidence of PONV after cataract surgery under general anaesthesia. The combination of both drugs revealed no additional effect.
The rat is an important animal model for human diseases and is widely used in physiology. In this article we present a new strategy for gene discovery based on the production of ESTs from serially ...subtracted and normalized cDNA libraries, and we describe its application for the development of a comprehensive nonredundant collection of rat ESTs. Our new strategy appears to yield substantially more EST clusters per ESTs sequenced than do previous approaches that did not use serial subtraction. However, multiple rounds of library subtraction resulted in high frequencies of otherwise rare internally primed cDNAs, defining the limits of this powerful approach. To date, we have generated >200,000 3' ESTs from >100 cDNA libraries representing a wide range of tissues and developmental stages of the laboratory rat. Most importantly, we have contributed to approximately 50,000 rat UniGene clusters. We have identified, arrayed, and derived 5' ESTs from >30,000 unique rat cDNA clones. Complete information, including radiation hybrid mapping data, is also maintained locally at http://genome.uiowa.edu/clcg.html. All of the sequences described in this article have been submitted to the dbEST division of the NCBI.
Diminished activity of peroxisome proliferator-activated receptor-gamma (PPARgamma) may play a role in the pathogenesis of hypertension and vascular dysfunction. To better understand what genes are ...regulated by PPARgamma, an experimental data set was generated by microarray analysis, in duplicate, of pooled aortic mRNA isolated from mice treated for 21 days with a PPARgamma agonist (rosiglitazone) or vehicle. Of the 12,488 probe sets present on the array (Affymetrix MG-U74Av2), 181 were differentially expressed between groups according to a statistical metric generated using Affymetrix software. A significant correlation was observed between the microarray results and real-time RT-PCR analysis of 39 of these genes. Cluster analysis revealed 3 expression patterns, 29 transcripts of moderate abundance that were decreased (-93%) to very low levels, 106 transcripts that were downregulated (-42%), and 46 transcripts that were upregulated (+70%). Functional groups that were decreased included inflammatory response (-93%, n = 6), immune response (-86%, n = 7), and cytokines (-82%, n = 7). There was an overall upregulation in the oxidoreductase activity group (+47%, n = 9). Individually, six transcripts in this group were increased (+72%), and three were decreased (-34%). Fourteen of the genes map to regions in the rat genome that have been linked to increased blood pressure, and of 142 upstream regions analyzed, sequences resembling the DNA binding site for PPARgamma were identified in 101 of the differentially expressed genes.
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