Production of pure samples of 131mXe and 135Xe.

Pure samples of (131m)Xe, (133m)Xe, (133)Xe and (135)Xe facilitate the calibration and testing of noble gas sampler stations and related laboratory instrumentation. We have earlier reported a Penning trap-based production method for pure (133m)Xe and (133)Xe samples. Here we complete the work by reporting the successful production of pure (131m)Xe and (135)Xe samples using the same technique. In addition, we present data on xenon release from graphite.

Continuous wound infusion with ropivacaine fails to provide adequate analgesia after caesarean section.

BACKGROUND: Continuous wound infusion with local anaesthetic has been used in post-caesarean pain management with conflicting results. We carried out a study comparing three groups: continuous ropivacaine wound infusion, intrathecal morphine with saline wound infusion and saline wound infusion only. METHODS: Sixty-six women undergoing elective caesarean section under combined spinal-epidural anaesthesia were randomly allocated to receive intrathecal morphine with saline wound infusion or 48 h continuous wound infusion with either ropivacaine or saline. All parturients received oral ketoprofen and intravenous oxycodone patient-controlled analgesia. Consumption of oxycodone, visual analogue scale pain scores (0-10 cm), patient satisfaction, side effects and recovery parameters were recorded for 48 h in a double-blind manner. RESULTS: Continuous wound infusion with ropivacaine failed to reduce oxycodone consumption or pain scores compared with saline control. In the first 24 h intrathecal morphine reduced mean oxycodone consumption compared to the ropivacaine wound infusion group (26 mg vs. 48 mg, P=0.007) and saline wound infusion group (26 mg vs. 45 mg, P=0.021). The first 24-h mean pain score was also lower in the intrathecal morphine group vs. the saline wound infusion group (1.3 vs. 2.2, P=0.021). Pain scores were not significantly different between intrathecal morphine and ropivacaine wound infusion groups. Pruritus was more common with intrathecal morphine. CONCLUSION: Compared to saline control, continuous wound infusion with ropivacaine failed to reduce the use of intravenous oxycodone patient-controlled analgesia or pain scores. Intrathecal morphine decreased oxycodone consumption by 46% in the first 24 h after surgery when compared to continuous ropivacaine wound infusion.

Determination of 239Pu/240Pu isotopic ratio by high-resolution alpha-particle spectrometry using the ADAM program.

A novel analysis program to unfold alpha-particle energy spectra was introduced, demonstrated and validated using radiochemically processed test sources, which contained different amounts of (239)Pu and (240)Pu. A high-resolution alpha spectrometer was used for data acquisition. The software known as ADAM unfolds the spectra using nuclide-specific decay data as a constraint. The peaks can have different shapes and the software can also cope with the coincidences between alpha particles and electrons/photons. In the present paper, the (239)Pu/(240)Pu activity ratios from alpha spectrometry agreed, within the stated uncertainties, with the reference values. Number of counts in the (239,240)Pu peak group must be larger than 100 to obtain reliable values when using semiconductor detector of energy resolution FWHM=10.6 keV.

Comparison of gamma-ray coincidence and low-background gamma-ray singles spectrometry.

Aerosol samples have been studied under different background conditions using gamma-ray coincidence and low-background gamma-ray singles spectrometric techniques with High-Purity Germanium detectors. Conventional low-background gamma-ray singles counting is a competitive technique when compared to the gamma-gamma coincidence approach in elevated background conditions. However, measurement of gamma-gamma coincidences can clearly make the identification of different nuclides more reliable and efficient than using singles spectrometry alone. The optimum solution would be a low-background counting station capable of both singles and gamma-gamma coincidence spectrometry.

Ultra-high resolution mass separator--application to detection of nuclear weapons tests.

A Penning trap-based purification process having a resolution of about 1 ppm is reported. In this context, we present for the first time a production method for the most complicated and crucially important nuclear weapons test signature, (133m)Xe. These pure xenon samples are required by the Comprehensive Nuclear-Test-Ban Treaty Organization to standardize and calibrate the worldwide network of xenon detectors.

Design of an air sampler for a small unmanned aerial vehicle.

In the aftermath of a nuclear accident or malevolent act, it is of paramount importance to have the capability to monitor airborne radioactive substances by collecting air samples. For potentially dangerous missions, the Radiation and Nuclear Safety Authority of Finland (STUK) has developed an air sampler to be used on a small unmanned aerial vehicle. When a Petrianov or Fluoropore filter is used in the sampler and the air velocity is 71 km h(-1), the air flow rate through the filter is 0.73 m(3) h(-1) or 0.23 m(3) h(-1), respectively. The present article introduces the developed air sampler using fluid dynamic simulations and wind tunnel data. The operation of the system was validated by collecting airborne radioactive aerosols from air.

The decay of 133mXe.

The decay of (133m)Xe has been re-measured using an electron-transporter spectrometer and a planar HPGe detector. The sample of (133m)Xe was produced by means of proton-induced fission using an ion-guide based on-line mass separator. The deduced K and L+M+... shell conversion coefficients, alpha(Kappa)=6.5(9) and alpha(L+M+...)=2.9(4), agree within the uncertainty limits with the theoretical values and remove the inconsistencies between the previous experimental studies of (133m)Xe.

Genetic variability of fragmented stands of pedunculate oak (Quercus robur) in Finland.

The genetic structure of 33 natural Quercus robur stands in Finland was studied using 13 allozyme loci to analyze the effects of fragmentation in a wind-pollinated tree species. The present fragmented and discontinuous distribution of oak is a result of both short-term human impact and long-term climatic and geological change, including post-glacial land uplift. In accordance with general expectations, genetic diversity in small populations was lower than that in large populations, and differentiation among small populations was higher than that among large populations. Heterozygote deficiency was more pronounced in large populations, which is proposed to be a Wahlund effect created by either spatial sub-structuring or the existence of synchronized flowering lineages. Also genetic differentiation was higher and diversity lower in Finland than the estimates reported for Central Europe. There were differences in the genetic structure on sites of different geological age. We suggest that on most geologically old sites drift has a prominent effect whereas on younger sites also founder effects may be important.

The electrocardiographic and hemodynamic effect of metohexital and propofol with and without esmolol.

BACKGROUND: Metohexital and propofol are short-acting induction agents, which have a tendency to prolong the QTc interval of the ECG. We studied whether this increase could be prevented by combining a beta-blocking agent, esmolol, with these drugs. Simultaneously, we studied the hemodynamic effects of these combinations. METHODS: In a randomized, double-blind study, 80 ASA I-II young adults were premedicated with oxycodone and atropin and allocated to one of four groups: propofol (P), propofol + esmolol (P + E), metohexital (E) or metohexital + esmolol (M + E). The doses were 2 mg/kg propofol/metohexital and 1 mg/kg esmolol. Alfentanil 15 microg/kg was used in all groups. The hemodynamic parameters were measured non-invasively and the electrocardiographic parameters using the signal processing method. RESULT: The highest QTc values, which often exceeded the normal upper limit of 440 ms, were recorded at the baseline or immediately after the administration of the induction drugs. The intervals were significantly shorter if esmolol was co-administered with either propofol or metohexital. The heart rate increased in the group M and decreased in the group P + E but remained unchanged in the groups P and M + E. Systolic and diastolic arterial pressures decreased during the study in all groups, most prominently in group P + E. CONCLUSIONS: During the anesthesia induction, the QTc interval was significantly shorter when esmolol was co-administered with either propofol or metohexital. The hemodynamic responses were properly controlled with the combination of metohexital and esmolol as well as with propofol alone, but the combination of propofol and esmolol tended to cause hemodynamic depression.

An empirical comparison of case-control and trio based study designs in high throughput association mapping.

Motivated by high throughput genotyping technology, our aim in this study was to experimentally compare the power and accuracy of case-control and family trio based approaches for haplotype based, large scale, association gene mapping. We compared trio based and case-control study designs in different disease models, and partitioned the performance differences into separate components: those from the sample ascertainment, the effective sample size, and the haplotyping approaches. For systematic and controlled tests, we simulated a rapidly expanding and relatively young isolated population. The experiments were also replicated with real asthma data. We used computationally efficient methods that scale up to large amounts of both markers and individuals. Mapping is based on a haplotype association test for haplotypes of 1-10 markers. For population based haplotype reconstruction, we use HaploRec, and compare it to both a simple trio based inference and true haplotypes. Firstly and surprisingly, statistically inferred population based haplotypes can be equally powerful as true haplotypes. Secondly, as expected, the effective sample size has a clear effect on both gene detection power and mapping accuracy. Thirdly, the sample ascertainment method does not have much effect on mapping accuracy. Finally, an interesting side result is that the simple haplotype association test clearly outperformed exhaustive allelic transmission disequilibrium tests. The results suggest that the case-control design is a powerful alternative to the more laborious family based ascertainment approach, especially for large datasets, and wherever population stratification can be controlled.

A Markov chain approach to reconstruction of long haplotypes.

Haplotypes are important for association based gene mapping, but there are no practical laboratory methods for obtaining them directly from DNA samples. We propose simple Markov models for reconstruction of haplotypes for a given sample of multilocus genotypes. The models are aimed specifically for long marker maps, where linkage disequilibrium between markers may vary and be relatively weak. Such maps are ultimately used in chromosome or genome-wide association studies. Haplotype reconstruction with standard Markov chains is based on linkage disequilibrium (LD) between neighboring markers. Markov chains of higher order can capture LD in a neighborhood of a given size. We introduce a more flexible and robust model, MC-VL, which is based on a Markov chain of variable order. Experimental validation of the Markov chain methods on both a wide range of simulated data and real data shows that they clearly out perform previous methods on genetically long marker maps and are highly competitive with short maps, too. MC-VL performs well across different data sets and settings while avoiding the problem of manually choosing an appropriate order for the Markov chain, and it has low computational complexity.

Association analysis for quantitative traits by data mining: QHPM.

Previously, we have presented a data mining-based algorithmic approach to genetic association analysis, Haplotype Pattern Mining. We have now extended the approach with the possibility of analysing quantitative traits and utilising covariates. This is accomplished by using a linear model for measuring association. We present results with the extended version, QHPM, with simulated quantitative trait data. One data set was simulated with the population simulator package Populus, and another was obtained from GAW12. In the former, there were 2-3 underlying susceptibility genes for a trait, each with several ancestral disease mutations, and 1 or 2 environmental components. We show that QHPM is capable of finding the susceptibility loci, even when there is strong allelic heterogeneity and environmental effects in the disease models. The power of finding quantitative trait loci is dependent on the ascertainment scheme of the data: collecting the study subjects from both ends of the quantitative trait distribution is more effective than using unselected individuals or individuals ascertained based on disease status, but QHPM has good power to localize the genes even with unselected individuals. Comparison with quantitative trait TDT (QTDT) showed that QHPM has better localization accuracy when the gene effect is weak.

A second-generation association study of the 5q31 cytokine gene cluster and the interleukin-4 receptor in asthma.

We have analyzed a dense set of single-nucleotide polymorphisms (SNPs) and microsatellites spanning the T-helper cytokine gene cluster (interleukins 3, 4, 5, 9, and 13, interferon regulatory factor-1, colony-stimulating factor-2, and T-cell transcription factor-7) on 5q31 and the gene encoding the interleukin-4 receptor (IL4R) on 16p12 among Finnish families with asthma. As shown by haplotype pattern mining analysis, the number of disease-associated haplotype patterns differed from that expected for the 129Q allele polymorphism in IL13 for high serum total immunoglobulin (Ig) E levels, but not for asthma. The same SNP also yielded the best haplotype associations. For IL4R, asthma-associated haplotype patterns, most spanning the S411L polymorphism, showed suggestive association. However, these haplotypes consisted of the major alleles for the intracellular part of the receptor and were very common among both patients and controls. The minor alleles 503P and 576R have been reported to be associated with decreased serum IgE levels and changes in the biological activity of the protein, especially when inherited together. In the Finnish population, these two polymorphisms segregated in strong linkage disequilibrium. Our data support previous findings regarding L4R, indicating that 503P and 576R may act as minor protecting alleles for IgE-mediated disorders.

L-Arginine in lung graft preservation and reperfusion.

BACKGROUND: Inhaled nitric oxide has been shown to ameliorate early lung graft dysfunction. It improves oxygenation by inducing pulmonary vasodilatation in well-ventilated lung areas, and it also modulates leukocyte-endothelium interactions. We used a porcine, single lung transplantation model to evaluate whether the benefits of exogenously administered gas could be achieved easier by adding L-arginine, the substrate of endogenous nitric oxide synthesis, as an additive to the flush solution and intravenously during reperfusion. METHODS: Six pig lungs were flushed with modified Euro-Collins solutions containing L-arginine (2 g/liter). After cold (4 degrees C) storage, the left lung was transplanted. Ischemic time was 260 minutes. The recipients received intravenous boluses of L-arginine (30 mg/kg), followed by infusion (20 mg/kg/min) during the first 30 minutes of reperfusion. Six control animals received saline as placebo. We measured the blood flow and pulmonary vascular resistance (PVR) in the transplanted and in the native lung using a right heart bypass model. We measured blood gases, leukocyte counts, plasma free-radical trapping capacity, and diene conjugates in pulmonary venous blood and myeloperoxidase activity of the lung tissue. RESULTS: Pulmonary vascular resistance was 4 to 5-fold higher in the transplanted lung than in the native lung, which received 80% of the total blood flow. L-arginine reduced PVR by 30% in the native lung (p < 0.001), but not in the transplanted lung. L-arginine had no effect on oxygenation or carbon dioxide exchange of the transplanted lung. Nor did L-arginine treatment have any effect on leukocyte sequestration or myeloperoxidase activity in the transplanted lung. The plasma antioxidant capacity in venous blood of the transplanted lung almost doubled shortly during early reperfusion without influence of L-arginine. CONCLUSIONS: L-arginine reduced PVR in the native lung but did not improve pulmonary hemodynamics, gas exchange, or reduce leukocyte sequestration of the transplanted lung.

Inhaled NO and prostacyclin during porcine single lung transplantation.

BACKGROUND: Increased pulmonary vascular resistance (PVR) and decreased arterial oxygenation frequently complicate lung transplantation. Inhaled nitric oxide (NO) and aerosolized prostacyclin (PGI2) both dilate the pulmonary vasculature and improve oxygenation in adult respiratory distress syndrome. We investigated whether similar effects would occur during early reperfusion of a lung graft. METHODS: Eighteen pigs underwent left lung transplantation. We measured blood flow distribution, mean pulmonary artery pressure, PVR, and gas exchange in each lung separately. Animals were randomized into three groups to receive NO (10 ppm/30 minutes, 40 ppm/30 minutes), nebulized PGI2 (25 microg/mL/30 minutes, 50 microg/mL/30 minutes), or no drugs (control). RESULTS: In the transplanted lung, PVR was significantly higher than in the native lung. Pulmonary vascular resistance of the transplanted lung was lower in the NO and PGI2 groups in comparison with the control group. During the first hour of inhalation, NO decreased PVR more than PGI2. Neither drug improved oxygenation in the graft. CONCLUSIONS: Nitric oxide and PGI2 decreased PVR of the transplanted lung slightly, but the effect did not produce a normal pressure in pulmonary vasculature.

Mining associations between genetic markers, phenotypes, and covariates.

We used Haplotype Pattern Mining, HPM [Toivonen et al., Am J Hum Genet 67:133-45, 2000], for gene localization in Genetic Analysis Workshop (GAW) 12 isolate data. In HPM, association is analyzed by searching all trait-associated haplotype patterns. Data mining algorithms are utilized to make the search efficient. The strength of the haplotype-trait associations is measured by a linear model, into which a pre-seelected set of covariates is incorporated. Marker-wise patterns of association are used for predicting the disease gene location. Genome-wide scans of susceptibility genes for affection status as well as for the quantitative traits (Q1-Q5) were performed. First analyses were made with small sample sizes, 63-94 trios per trait, which is compared with a pilot study of a larger complex disease-mapping project. Subsequently, the analysis was repeated with approximately 600 cases and 600 controls per trait to give higher power to the analyses. With small sample sizes, only the susceptibility genes having the strongest effects on the traits could be localized. The larger sample size gave very good results: all susceptibility genes, except one, could be correctly localized. First experiments on candidate genes suggested that HPM is applicable even to fine mapping of mutations in DNA sequence.

The effect of nitecapone on early graft function in experimental single lung transplantation.

Nitecapone is an antioxidant molecule which has been shown to protect the heart against ischemia-reperfusion injury. We investigated whether a similar effect could be detected on lung graft preservation in a porcine model of single lung transplantation. Donors received either nitecapone or placebo in a modified Euro-Collins pulmonary flush solution. After cold storage for 19 h the left lung was transplanted. Patients in the nitecapone group received a nitecapone infusion during the graft reperfusion. A right-side heart bypass was used to measure flow distribution and pulmonary vascular resistance (PVR) in the recipient's transplanted and native lungs, respectively. Pulmonary vein blood samples were analyzed for blood gases, free radical trapping capacity and diene conjugates. PVR was high in the transplanted lung, which received only 20% of the blood flow. Oxygen tension in the transplanted lung was low (2.3-26.7 kPa). Nitecapone treatment increased the plasma free radical trapping capacity threefold. In spite of this increase in antioxidative capacity nitecapone could not protect the lung against ischemia-reperfusion injury when pulmonary hemodynamics, gas exchange or plasma diene conjugates were used as measures of lung graft function.

Anaesthesia for patients with a transplanted organ.

Increasing numbers of individuals leading normal lives have transplanted organs. They may appear in any hospital for treatment of trauma or general diseases. Common anaesthesia methods can be used for these patients, but safe conduct of anaesthesia requires knowledge of the immunosuppression, risk factors, and altered physiology or drug actions. This article reviews the anaesthesia-related literature on patients with transplanted organs.

Data mining applied to linkage disequilibrium mapping.

We introduce a new method for linkage disequilibrium mapping: haplotype pattern mining (HPM). The method, inspired by data mining methods, is based on discovery of recurrent patterns. We define a class of useful haplotype patterns in genetic case-control data and use the algorithm for finding disease-associated haplotypes. The haplotypes are ordered by their strength of association with the phenotype, and all haplotypes exceeding a given threshold level are used for prediction of disease susceptibility-gene location. The method is model-free, in the sense that it does not require (and is unable to utilize) any assumptions about the inheritance model of the disease. The statistical model is nonparametric. The haplotypes are allowed to contain gaps, which improves the method's robustness to mutations and to missing and erroneous data. Experimental studies with simulated microsatellite and SNP data show that the method has good localization power in data sets with large degrees of phenocopies and with lots of missing and erroneous data. The power of HPM is roughly identical for marker maps at a density of 3 single-nucleotide polymorphisms/cM or 1 microsatellite/cM. The capacity to handle high proportions of phenocopies makes the method promising for complex disease mapping. An example of correct disease susceptibility-gene localization with HPM is given with real marker data from families from the United Kingdom affected by type 1 diabetes. The method is extendable to include environmental covariates or phenotype measurements or to find several genes simultaneously.

Successful treatment of mediastinal gas gangrene due to esophageal perforation.

Esophageal perforation and mediastinal gas gangrene developed in a 55-year-old male after the endoscopic ethanol injection of a Mallory-Weiss ulcer. Initially, extensive gangrene of the esophagus and the mediastinum was treated by esophagectomy; however, an abundance of Clostridium perfringens in the Gram stain verified the presence of gas gangrene. Subsequently, the patient was transferred to a hyperbaric oxygen center, wherein a total of seven hyperbaric treatments were administered. The patient survived, and 4 months later, after having undergone several reoperations because of pleural empyema, mediastinal abscess, splenic rupture, and acalculous cholecystitis, was discharged and is still surviving.