| 1. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 9. |
- Okhuijsen-Pfeifer, C, et al.
(författare)
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Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders
- 2022
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 145-
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Tidskriftsartikel (refereegranskat)abstract
- Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10−3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10−4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10−3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10−7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.
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| 12. |
- Astuto, L. M., et al.
(författare)
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CDH23 mutation and phenotype heterogeneity : a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness
- 2002
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 71:2, s. 262-275
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Tidskriftsartikel (refereegranskat)abstract
- Usher syndrome type I is characterized by congenital hearing loss, retinitis pigmentosa (RP), and variable vestibular areflexia. Usher syndrome type ID, one of seven Usher syndrome type I genetic localizations, have been mapped to a chromosomal interval that overlaps with a nonsyndromic-deafness localization, DFNB12. Mutations in CDH23, a gene that encodes a putative cell-adhesion protein with multiple cadherin-like domains, are responsible for both Usher syndrome and DFNB12 nonsyndromic deafness. Specific CDH23 mutational defects have been identified that differentiate these two phenotypes. Only missense mutations of CDH23 have been observed in families with nonsyndromic deafness, whereas nonsense, frameshift, splice-site, and missense mutations have been identified in families with Usher syndrome. In the present study, a panel of 69 probands with Usher syndrome and 38 probands with recessive nonsyndromic deafness were screened for the presence of mutations in the entire coding region of CDH23, by heteroduplex, single-strand conformation polymorphism, and direct sequence analyses. A total of 36 different CDH23 mutations were detected in 45 families; 33 of these mutations were novel, including 18 missense, 3 nonsense, 5 splicing defects, 5 microdeletions, and 2 insertions. A total of seven mutations were common to more than one family. Numerous exonic and intronic polymorphisms also were detected. Results of ophthalmologic examinations of the patients with nonsyndromic deafness have found asymptomatic RP-like manifestations, indicating that missense mutations may have a subtle effect in the retina. Furthermore, patients with mutations in CDH23 display a wide range of hearing loss and RP phenotypes, differing in severity, age at onset, type, and the presence or absence of vestibular areflexia.
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| 13. |
- Chiappa, V., et al.
(författare)
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Agreement of two-dimensional and three-dimensional transvaginal ultrasound with magnetic resonance imaging in assessment of parametrial infiltration in cervical cancer
- 2015
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 45:4, s. 459-469
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To compare two-dimensional (2D) and three-dimensional (3D) transvaginal ultrasound with magnetic resonance imaging (MRI) as the gold standard in assessment of parametrial infiltration of cervical cancer and to determine if all parts of the cervix are equally assessable with ultrasound. Methods Patients with macroscopically evident and histologically confirmed cervical cancer were staged using International Federation of Gynecology and Obstetrics (FIGO) criteria and underwent MRI and 2D and 3D ultrasound examination before treatment. When assessing parametrial infiltration with 3D ultrasound and MRI, the cervix was (virtually) divided into three cylinders (cranial, middle and caudal) of equal size and each cylinder was then divided into six sectors in a clockwise manner following a consensus between radiologists and ultrasound examiners. The presence and the extent of parametrial invasion were recorded for each sector. Results of 2D ultrasound, 3D ultrasound and MRI were compared and reported in terms of percentage agreement and kappa value. Results A total of 29 consecutive patients were included in the study. The percentage agreement between 2D ultrasound and MRI in assessing parametrial infiltration (yes or no) was 76% (kappa, 0.459) and that between 3D ultrasound and MRI was 79% (kappa, 0.508). The results of 2D ultrasound showed the following agreement with those of MRI: 90% for the ventral parametrium (kappa, 0.720), 72% for the right lateral parametrium kappa, 0.494), 69% for the left lateral parametrium (kappa, 0.412) and 58.5% for the dorsal parametrium (kappa, 0.017). The results of 3D ultrasound showed the following agreement with those of MRI: 62.5% for the ventral parametrium (kappa, 0.176), 81% for the right lateral parametrium (kappa, 0.595), 70% for the left lateral parametrium (kappa, 0.326) and 52% for the dorsal parametrium (kappa, 0.132). The best agreement between 3D ultrasound and MRI was for the middle cervical cylinder (76%; kappa, 0.438) and the poorest agreement was for the caudal cylinder (42%; kappa, 0.125). Conclusion The results of 2D and 3D ultrasound showed similar moderate agreement with MRI; 2D and 3D ultrasound examinations are less costly and more readily available than MRI and should be considered in the preoperative work-up for cervical cancer. Copyright (C) 2014 ISUOG. Published by John Wiley & Sons Ltd.
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| 14. |
- Di Legge, A., et al.
(författare)
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Lesion size affects diagnostic performance of IOTA logistic regression models, IOTA simple rules and risk of malignancy index in discriminating between benign and malignant adnexal masses
- 2012
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 40:3, s. 345-354
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To estimate the ability to discriminate between benign and malignant adnexal masses of different size using: subjective assessment, two International Ovarian Tumor Analysis (IOTA) logistic regression models (LR1 and LR2), the IOTA simple rules and the risk of malignancy index (RMI). Methods We used a multicenter IOTA database of 2445 patients with at least one adnexal mass, i.e. the database previously used to prospectively validate the diagnostic performance of LR1 and LR2. The masses were categorized into three subgroups according to their largest diameter: small tumors (diameter < 4 cm; n = 396), medium-sized tumors (diameter, 49.9 cm; n = 1457) and large tumors (diameter = 10 cm, n = 592). Subjective assessment, LR1 and LR2, IOTA simple rules and the RMI were applied to each of the three groups. Sensitivity, specificity, positive and negative likelihood ratio (LR+, LR-), diagnostic odds ratio (DOR) and area under the receiveroperating characteristics curve (AUC) were used to describe diagnostic performance. A moving window technique was applied to estimate the effect of tumor size as a continuous variable on the AUC. The reference standard was the histological diagnosis of the surgically removed adnexal mass. Results The frequency of invasive malignancy was 10% in small tumors, 19% in medium-sized tumors and 40% in large tumors; 11% of the large tumors were borderline tumors vs 3% and 4%, respectively, of the small and medium-sized tumors. The type of benign histology also differed among the three subgroups. For all methods, sensitivity with regard to malignancy was lowest in small tumors (5684% vs 6793% in medium-sized tumors and 7495% in large tumors) while specificity was lowest in large tumors (6087%vs 8395% in medium-sized tumors and 8396% in small tumors ). The DOR and the AUC value were highest in medium-sized tumors and the AUC was largest in tumors with a largest diameter of 711 cm. Conclusion Tumor size affects the performance of subjective assessment, LR1 and LR2, the IOTA simple rules and the RMI in discriminating correctly between benign and malignant adnexal masses. The likely explanation, at least in part, is the difference in histology among tumors of different size. Copyright (C) 2012 ISUOG. Published by John Wiley & Sons, Ltd.
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| 19. |
- Epstein, Elisabeth, et al.
(författare)
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Sonographic characteristics of squamous cell cancer and adenocarcinoma of the uterine cervix.
- 2010
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Ingår i: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. - : Wiley. - 1469-0705. ; Apr 8, s. 512-516
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe the sonographic characteristic of squamous cell cancer (SCC) and adenocarcinoma (AC) of the cervix using transvaginal ultrasound. METHODS: Women with early stage cervical cancer undergoing transvaginal ultrasound examination prior to surgery were prospectively included. The sonographic characteristics were assessed with regard to tumor morphology, vascularization, size, extension and location. Histological assessment of tumor subtype, size, growth pattern, extension, location was performed. Both sonographic and histological assessments were done according to a standardized protocol. RESULTS: Fifty-five women were recruited. Ten were excluded since no tumor was seen on ultrasound and 5 because radical surgery was aborted due to positive lymph nodes, detected by the sentinel node technique. Among the remaining 40 women 20 had AC and 20 SCC. At pathological examination 34 women had tumors confined to the cervix, 3 had parametrial and 3 vaginal invasion. Hypoechoic echogenicity was associated with SCC in 73% (11/15), while isoechoic echogenicity indicated AC in 68% (13/19) of the women (p=0.03). Mixed echogenicity (n=4) showed a non-significant relation to larger tumor volume (p=0.23). Hyperechoic echogenicity was found in 2 women, both with the less malignant villoglandular AC. Color Doppler signals were found in all AC and 90% (18/20) of the SCC, as compared to most normal cervical tissue with virtually no detectable vascularization. CONCLUSIONS: We found that the sonographic appearance of SCC and AC differs, a knowledge that can be of use in the clinical evaluation of cervical tumors. Copyright (c) 2010 ISUOG. Published by John Wiley & Sons, Ltd.
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| 20. |
- Gaurilcikas, A., et al.
(författare)
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Early-stage cervical cancer: agreement between ultrasound and histopathological findings with regard to tumor size and extent of local disease
- 2011
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 38:6, s. 707-715
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To determine the agreement between ultrasound and histological examination of the cervix in patients with early stage cervical cancer with regard to tumor size and local extent of the disease. Methods Eighteen patients with histologically proven cervical cancer Stage IB1-IIA according to traditional clinical staging (FIGO 1988) who were scheduled for radical surgery underwent a standardized transvaginal ultrasound examination. The maximum tumor length, anteroposterior tumor diameter, tumor width, tumor area, depth of cervical stroma invasion, and the minimal thickness of tumor-free cervical stroma on sagittal and transverse planes through the cervix were measured, and the local extent of the disease within the parametria and vagina were evaluated. The surgical specimens were examined using a specifically devised method of histopathological examination. The results of the ultrasound and histopathological examinations were compared. Results Limits of agreement were wide and the intra-class correlation coefficient (ICC) was low (0.51-0.58) for three of the four measurements taken to represent the minimal depth of tumor-free cervical stroma, i.e. the results of the measurements taken posteriorly and laterally. However, the limits of agreement were narrower and the ICC values were higher (0.74-0.92) for the depth of cervical stroma invasion and for the tumor size measurements. Histological examination revealed parametrial cancer infiltration in four patients, which was detected during ultrasound examination, with no false-positive results. Conclusions Transvaginal sonography is acceptably accurate for evaluation of tumor size and depth of cervical stroma invasion in clinical practice. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.
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| 21. |
- Legge, Alexandra, et al.
(författare)
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Construction of a frailty index as a novel health measure in systemic lupus erythematosus
- 2020
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 47:1, s. 72-81
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To construct a Frailty Index (FI) as a measure of vulnerability to adverse outcomes among patients with systemic lupus erythematosus (SLE), using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Methods. The SLICC inception cohort consists of recently diagnosed patients with SLE followed annually with clinical and laboratory assessments. For this analysis, the baseline visit was defined as the first study visit at which sufficient information was available for construction of an FI. Following a standard procedure, variables from the SLICC database were evaluated as potential health deficits. Selected health deficits were then used to generate a SLICC-FI. The prevalence of frailty in the baseline dataset was evaluated using established cutpoints for FI values. Results. The 1683 patients with SLE (92.1% of the overall cohort) eligible for inclusion in the baseline dataset were mostly female (89%) with mean (SD) age 35.7 (13.4) years and mean (SD) disease duration 18.8 (15.7) months at baseline. Of 222 variables, 48 met criteria for inclusion in the SLICC-FI. Mean (SD) SLICC-FI was 0.17 (0.08) with a range from 0 to 0.51. At baseline, 27.1% (95% CI 25.0-29.2) of patients were classified as frail, based on SLICC-FI values > 0.21. Conclusion. The SLICC inception cohort permits feasible construction of an FI for use in patients with SLE. Even in a relatively young cohort of patients with SLE, frailty was common. The SLICC-FI may be a useful tool for identifying patients with SLE who are most vulnerable to adverse outcomes, but validation of this index is required prior to its use.
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| 22. |
- Legge, Alexandra, et al.
(författare)
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Prediction of Damage Accrual in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index
- 2020
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Ingår i: Arthritis and Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 72:4, s. 658-666
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC FI values with damage accrual in the SLICC inception cohort. Methods: The baseline visit was defined as the first visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short Form 36) were assessed. Baseline SLICC FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression was used to estimate the association between baseline SLICC FI values and the rate of increase in the SDI during follow-up, adjusting for relevant demographic and clinical characteristics. Results: The 1,549 systemic lupus erythematosus (SLE) patients eligible for this analysis were mostly female (88.7%) with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9–1.5 years) at baseline. The mean ± SD baseline SLICC FI was 0.17 ± 0.08. Over a mean ± SD follow-up of 7.2 ± 3.7 years, 653 patients (42.2%) had an increase in SDI. Higher baseline SLICC FI values (per 0.05 increase) were associated with higher rates of increase in the SDI during follow-up (incidence rate ratio [IRR] 1.19 [95% confidence interval 1.13–1.25]), after adjusting for age, sex, ethnicity/region, education, baseline SLE Disease Activity Index 2000, baseline SDI, and baseline use of glucocorticoids, antimalarials, and immunosuppressive agents. Conclusion: Our findings indicate that the SLICC FI predicts damage accrual in incident SLE, which further supports the SLICC FI as a valid health measure in SLE.
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| 23. |
- Legge, Alexandra, et al.
(författare)
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Prediction of Hospitalizations in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index
- 2022
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-464X .- 2151-4658. ; 74:4, s. 638-647
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in systemic lupus erythematosus (SLE), but its association with hospitalizations has not been described. Our objective was to estimate the association of baseline SLICC-FI values with future hospitalizations in the SLICC inception cohort. Methods: Baseline SLICC-FI scores were calculated. The number and duration of inpatient hospitalizations during follow-up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC-FI values and the rate of hospitalizations per patient-year of follow-up. Linear regression was used to estimate the association of baseline SLICC-FI scores with the proportion of follow-up time spent in the hospital. Multivariable models were adjusted for relevant baseline characteristics. Results: The 1,549 patients with SLE eligible for this analysis were mostly female (88.7%), with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9–1.5) at baseline. Mean ± SD baseline SLICC-FI was 0.17 ± 0.08. During mean ± SD follow-up of 7.2 ± 3.7 years, 614 patients (39.6%) experienced 1,570 hospitalizations. Higher baseline SLICC-FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow-up, with an incidence rate ratio of 1.21 (95% confidence interval [95% CI] 1.13–1.30) after adjustment for baseline age, sex, glucocorticoid use, immunosuppressive use, ethnicity/location, SLE Disease Activity Index 2000 score, SLICC/American College of Rheumatology Damage Index score, and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC-FI values predicted a greater proportion of follow-up time spent hospitalized (relative rate 1.09 [95% CI 1.02–1.16]). Conclusion: The SLICC-FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC-FI as a valid health measure in SLE.
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| 25. |
- Pardiñas, Antonio F., et al.
(författare)
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Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia
- 2022
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Ingår i: JAMA psychiatry. - Chicago, IL, United States : American Medical Association. - 2168-6238 .- 2168-622X. ; 79:3, s. 260-269
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Tidskriftsartikel (refereegranskat)abstract
- Importance About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts.Objective To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples.Design, Setting, and Participants Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]).Main Outcomes and Measures GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition.Results The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P = .04).Conclusions and Relevance In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance.
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| 26. |
- Piletsky, SA, et al.
(författare)
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Recognition of ephedrine enantiomers by molecularly imprinted polymers designed using a computational approach
- 2001
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Ingår i: The Analyst. - : Royal Society of Chemistry. - 0003-2654 .- 1364-5528. ; 126:10, s. 1826-1830
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Tidskriftsartikel (refereegranskat)abstract
- A new approach to the computational design of molecularly imprinted polymers (MIP) specific for ephedrine is presented. A virtual library of functional monomers was developed and screened against the template using molecular modelling software. The monomers giving the highest binding score were co-polymerized with a cross-linker in the presence of ephedrine. Control (blank) polymers were prepared under the same conditions but in the absence of the template. A good correlation was found between the modelling results and performance of the materials in an HPLC study. A MIP based on one of the selected monomers-hydroxyethyl methacrylate-gave a separation of ephedrine enantiomers with a separation factor a of 1.42-2.09 (depending on temperature). This figure is larger than the a values generally obtained with commercially available chiral phases. It is anticipated that the computational approach will be of use for the rational design of MIPS and the prediction of polymer affinity and specificity.
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| 27. |
- Schuster, U., et al.
(författare)
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Measurements of total alkalinity and inorganic dissolved carbon in the Atlantic Ocean and adjacent Southern Ocean between 2008 and 2010
- 2014
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 6:1, s. 175-183
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Tidskriftsartikel (refereegranskat)abstract
- Water column dissolved inorganic carbon and total alkalinity were measured during five hydrographic sections in the Atlantic Ocean and Drake Passage. The work was funded through the Strategic Funding Initiative of the UK's Oceans2025 programme, which ran from 2007 to 2012. The aims of this programme were to establish the regional budgets of natural and anthropogenic carbon in the North Atlantic, the South Atlantic, and the Atlantic sector of the Southern Ocean, as well as the rates of change of these budgets. This paper describes in detail the dissolved inorganic carbon and total alkalinity data collected along east-west sections at 47 degrees N to 60 degrees N, 24.5 degrees N, and 24 degrees S in the Atlantic and across two Drake Passage sections. Other hydrographic and biogeochemical parameters were measured during these sections, and relevant standard operating procedures are mentioned here. Over 95% of dissolved inorganic carbon and total alkalinity samples taken during the 24.5 degrees N, 24 degrees S, and the Drake Passage sections were analysed onboard and subjected to a first-level quality control addressing technical and analytical issues. Samples taken along 47 degrees N to 60 degrees N were analysed and subjected to quality control back in the laboratory. Complete post-cruise second-level quality control was performed using crossover analysis with historical data in the vicinity of measurements, and data were submitted to the CLIVAR and Carbon Hydrographic Data Office (CCHDO), the Carbon Dioxide Information Analysis Center (CDIAC) and and will be included in the Global Ocean Data Analyses Project, version 2 (GLODAP 2), the upcoming update of Key et al. (2004).
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| 30. |
- Zannoni, L, et al.
(författare)
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Intra- and inter-observer reproducibility of assessment of Doppler ultrasound findings in adnexal masses.
- 2013
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 42:1, s. 93-101
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To estimate intra- and inter-observer reproducibility and reliability of assessment of the color content in adnexal masses at color/power Doppler ultrasound examination for observers with different levels of experience, and to determine if they change after a consensus meeting. Methods: Digital clips with color/power Doppler information of 103 adnexal masses were evaluated independently four times, twice before and twice after a consensus meeting, by four experienced and three less experienced ultrasound examiners. The color content of the adnexal mass was estimated using the International Ovarian Tumor Analysis color score and a 100 mm visual analogue scale (VAS score). Intraobserver repeatability was estimated for each observer. Interobserver agreement was estimated for the four most experienced observers (six pairs), for the three less experienced observers (three pairs), and for four other pairs of observers, each pair consisting of one of the experienced and one of the less-experienced observers. Results: Intra- and inter-observer agreement for the color score was moderate to very good, percentage agreement ranging from 48% to 82.5% (Kappa 0.52-0.82) before and from 59% to 90% (Kappa 0.60-0.88) after the consensus meeting. For seven of 13 pairs of observers, interobserver agreement improved after the consensus meeting. Intra-observer intraclass correlation coefficient (ICC) values for the VAS score ranged from 0.80 to 0.92 before and from 0.75 to 0.94 after the consensus meeting, but limits of agreement were wide (+/-20-35 mm). For six of the seven observers the ICC values were higher after the consensus meeting than before. Inter-observer ICC values for the VAS score ranged from 0.77 to 0.88 before and from 0.77 to 0.91 after the consensus meeting, but limits of agreement were wide (+/-30-40 mm). For ten of 13 pairs of observers the ICC values improved after the consensus meeting. Conclusions: Intra-and inter-observer agreement for the color score was good, especially after the consensus meeting, but there is room for improvement. VAS score results varied substantially within and between observers both before and after the consensus meeting. General consensus needs to be reached about how to interpret color/power Doppler ultrasound findings in adnexal masses. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
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