| 1. |
- Appelblad, P.K., et al.
(författare)
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Sources of uncertainty in isotope ratio measurements by inductively coupled plasma mass spectrometry
- 2001
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 73:13, s. 2911-2919
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Tidskriftsartikel (refereegranskat)abstract
- A model is presented describing the effects of dead time and mass bias correction factor uncertainties, flicker noise, and counting statistics on isotope ratio measurement precision using inductively coupled plasma mass spectrometry (ICPMS) with a single collector. Noise spectral analysis is exploited to enable estimation of the flicker noise parameters. For the instrument used, the flicker noise component exhibited a fairly weak frequency (f) dependence ( f -0.33±0.12), but was directly proportional to the total number of counts, Q. As white noise, determined by counting statistics, is given by Q0.5, the isotope ratio measurement uncertainties will actually cease to improve when Q exceeds a certain threshold. This would suggest that flicker noise could become the limiting factor for the precision with which isotope ratios can be determined by ICPMS. However, under most experimental conditions, uncertainties associated with mass discrimination and dead time correction factors are decisive. For ratios up to ~22 (115In/113In), optimum major isotope count rates are generally below 0.3 MHz, for which precision in the mass discrimination factor is limiting. The model derived could be used as a starting point for determining optimum conditions and understanding the limitations of single-collector ICPMS for precise isotope ratio measurements.
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| 2. |
- Astuti, D, et al.
(författare)
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Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma.
- 2001
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 69:1, s. 49-54
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Tidskriftsartikel (refereegranskat)abstract
- The pheochromocytomas are an important cause of secondary hypertension. Although pheochromocytoma susceptibility may be associated with germline mutations in the tumor-suppressor genes VHL and NF1 and in the proto-oncogene RET, the genetic basis for most cases of nonsyndromic familial pheochromocytoma is unknown. Recently, pheochromocytoma susceptibility has been associated with germline SDHD mutations. Germline SDHD mutations were originally described in hereditary paraganglioma, a dominantly inherited disorder characterized by vascular tumors in the head and the neck, most frequently at the carotid bifurcation. The gene products of two components of succinate dehydrogenase, SDHC and SDHD, anchor the gene products of two other components, SDHA and SDHB, which form the catalytic core, to the inner-mitochondrial membrane. Although mutations in SDHC and in SDHD may cause hereditary paraganglioma, germline SDHA mutations are associated with juvenile encephalopathy, and the phenotypic consequences of SDHB mutations have not been defined. To investigate the genetic causes of pheochromocytoma, we analyzed SDHB and SDHC, in familial and in sporadic cases. Inactivating SDHB mutations were detected in two of the five kindreds with familial pheochromocytoma, two of the three kindreds with pheochromocytoma and paraganglioma susceptibility, and 1 of the 24 cases of sporadic pheochromocytoma. These findings extend the link between mitochondrial dysfunction and tumorigenesis and suggest that germline SDHB mutations are an important cause of pheochromocytoma susceptibility.
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| 3. |
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| 4. |
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| 5. |
- Crabtree, Judy S, et al.
(författare)
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Of mice and MEN1 : Insulinomas in a conditional mouse knockout.
- 2003
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Ingår i: Molecular and Cellular Biology. - 0270-7306 .- 1098-5549. ; 23:17, s. 6075-6085
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Tidskriftsartikel (refereegranskat)abstract
- Patients with multiple endocrine neoplasia type 1 (MEN1) develop multiple endocrine tumors, primarily affecting the parathyroid, pituitary, and endocrine pancreas, due to the inactivation of the MEN1 gene. A conditional mouse model was developed to evaluate the loss of the mouse homolog, Men1, in the pancreatic beta cell. Men1 in these mice contains exons 3 to 8 flanked by loxP sites, such that, when the mice are crossed to transgenic mice expressing cre from the rat insulin promoter (RIP-cre), exons 3 to 8 are deleted in beta cells. By 60 weeks of age, >80% of mice homozygous for the floxed Men1 gene and expressing RIP-cre develop multiple pancreatic islet adenomas. The formation of adenomas results in elevated serum insulin levels and decreased blood glucose levels. The delay in tumor appearance, even with early loss of both copies of Men1, implies that additional somatic events are required for adenoma formation in beta cells. Comparative genomic hybridization of beta cell tumor DNA from these mice reveals duplication of chromosome 11, potentially revealing regions of interest with respect to tumorigenesis.
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| 6. |
- Douglas, K S, et al.
(författare)
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Evaluation of a model of violence risk assessment among forensic psychiatric patients
- 2003
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Ingår i: Psychiatric Services. - 1075-2730 .- 1557-9700. ; 54:10, s. 1372-1379
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study tested the interrater reliability and criterion-related validity of structured violence risk judgments made by using one application of the structured professional judgment model of violence risk assessment, the HCR-20 violence risk assessment scheme, which assesses 20 key risk factors in three domains: historical, clinical, and risk management. Methods: The HCR-20 was completed for a sample of 100 forensic psychiatric patients who had been found not guilty by reason of a mental disorder and were subsequently released to the community. Violence in the community was determined from multiple file-based sources. Results: Interrater reliability of structured final risk judgments of low, moderate, or high violence risk made on the basis of the structured professional judgment model was acceptable (weighted kappa=.61). Structured final risk judgments were significantly predictive of postrelease community violence, yielding moderate to large effect sizes. Event history analyses showed that final risk judgments made with the structured professional judgment model added incremental validity to the HCR-20 used in an actuarial (numerical) sense. Conclusions: The findings support the structured professional judgment model of risk assessment as well as the HCR-20 specifically and suggest that clinical judgment, if made within a structured context, can contribute in meaningful ways to the assessment of violence risk.
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| 7. |
- Douglas, K S, et al.
(författare)
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The impact of confidence on the accuracy of structured professional and actuarial violence risk judgments in a sample of forensic psychiatric patients
- 2003
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Ingår i: Law and human behavior. - 0147-7307 .- 1573-661X. ; 27:6, s. 573-587
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Tidskriftsartikel (refereegranskat)abstract
- Some previous research indicates that confidence affects the accuracy of probabilistic clinical ratings of risk for violence among civil psychiatric inpatients. The current study investigated the impact of confidence on actuarial and structured professional risk assessments, in a forensic psychiatric population, using community violence as the outcome criteria. Raters completed the HCR-20 violence risk assessment scheme for a sample of 100 forensic psychiatric patients. Results showed that accuracy of both actuarial judgments (HCR-20 total scores) and structured professional judgments (of low, moderate, and high risk) were substantially more accurate when raters were more confident about their judgments. Findings suggest that confidence of ratings should be studied as a potentially important mediator of structured professional and actuarial risk judgments.
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| 8. |
- Harang, Valérie, 1966-
(författare)
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Aspects of Optimisation of Separation of Drugs by Chemometrics
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Statistical experimental designs have been used for method development and optimisation of separation. Two reversed phase HPLC methods were optimised. Parameters such as the pH, the amount of tetrabutylammonium (TBA; co-ion) and the gradient slope (acetonitrile) were investigated and optimised for separation of erythromycin A and eight related compounds. In the second method, a statistical experimental design was used, where the amounts of acetonitrile and octane sulphonate (OSA; counter ion) and the buffer concentration were studied, and generation of an α-plot with chromatogram simulations optimised the separation of six analytes.The partial filling technique was used in capillary electrophoresis to introduce the chiral selector Cel7A. The effect of the pH, the ionic strength and the amount of acetonitrile on the separation and the peak shape of R- and S-propranolol were investigated.Microemulsion electrokinetic chromatography (MEEKC) is a technique similar to micellar electrokinetic chromatography (MEKC), except that the microemulsion has a core of tiny droplets of oil inside the micelles. A large number of factors can be varied when using this technique. A screening design using the amounts of sodium dodecyl sulphate (SDS), Brij 35, 1-butanol and 2-propanol, the buffer concentration and the temperature as factors revealed that the amounts of SDS and 2-propanol were the most important factors for migration time and selectivity manipulation of eight different compounds varying in charge and hydrophobicity. SDS and 2-propanol in the MEEKC method were further investigated in a three-level full factorial design analysing 29 different compounds sorted into five different groups. Different optimisation strategies were evaluated such as generating response surface plots of the selectivity/resolution of the most critical pair of peaks, employing chromatographic functions, simplex optimisation in MODDE and 3D resolution maps in DryLab™.Molecular descriptors were fitted in a PLS model to retention data from the three-level full factorial design of the MEEKC system. Two different test sets were used to study the predictive ability of the training set. It was concluded that 86 – 89% of the retention data could be predicted correctly for new molecules (80 – 120% of the experimental values) with different settings of SDS and 2-propanol.Statistical experimental designs and chemometrics are valuable tools for the development and optimisation of analytical methods. The same chemometric strategies can be employed for all types of separation techniques.
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| 9. |
- Harang, Valérie, et al.
(författare)
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Microemulsion electrokinetic chromatography of drugs varying in charge and hydrophobicity : I. Impact of parameters on separation performance evaluated by multiple linear regression models
- 2004
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Ingår i: Electrophoresis. - : Wiley. - 0173-0835 .- 1522-2683. ; 25:1, s. 80-93
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Tidskriftsartikel (refereegranskat)abstract
- The separation of anionic, cationic and neutral drugs in microemulsion electrokinetic chromatography (MEEKC) was studied with a statistical experimental design. The concentration of sodium dodecyl sulfate (SDS, surfactant), 1-butanol (co-surfactant) and borate buffer and the factors Brij 35 (surfactant), 2-propanol (organic solvent) and cassette temperature were varied simultaneously, while the parameters pH (9.2), the concentration of octane (oil, 0.8% w/w), the voltage (10 kV) and the dimension of the fused-silica capillary, were kept constant. Eight different model substances were chosen with different hydrophobicities. Two of the analytes were positively charged, two were negatively charged, and the remaining four were neutral or close to neutral at the pH explored. The importance of each parameter on the separation window, the plate height and the retention factor for each of the analytes was studied by means of multiple linear regression (MLR) models. A new response was evaluated for anions, the quotient between the effective mobility in the microemulsion and the effective mobility in the corresponding buffer. Factors affecting selectivity changes were also explored, and it was found that SDS and 2-propanol had the largest effect on selectivity.
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| 10. |
- Harang, Valérie, et al.
(författare)
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Microemulsion electrokinetic chromatography of drugs varying in charge and hydrophobicity : II. Strategies for optimisation of separation
- 2004
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Ingår i: Electrophoresis. - : Wiley. - 0173-0835 .- 1522-2683. ; 25:12, s. 1792-1809
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Tidskriftsartikel (refereegranskat)abstract
- The separation of anionic, cationic, and neutral drugs in microemulsion electrokinetic chromatography (MEEKC) was studied. The concentration of sodium dodecyl sulfate (SDS; surfactant) and 2-propanol (organic solvent) was varied in a three-level full factorial design. 29 different model substances were chosen with different hydrophobicities and charges (neutral, positive, and negative). The models were calculated by means of multiple linear regression (MLR). The compounds were divided into five different subgroups, and different strategies for optimization of the separation within each group were investigated. The optimization was done by maximizing the selectivity using response surface plots in MODDE, by calculation of different chromatographic functions, and by using the software DryLab. For all the different groups, MODDE, almost all chromatographic functions and DryLab gave approximately the same settings of the factors for optimum separation. Attempts were made to fit descriptors of the compounds to the retention data from the three-level full factorial design by means of partial least squares projection to latent structures (PLS). Between 86 and 89% of all predictions of migration times were acceptable (80-120% of the observed value).
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