| 31. |
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| 32. |
- Millischer, V., et al.
(författare)
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Improving lithium dose prediction using population pharmacokinetics and pharmacogenomics: a cohort genome-wide association study in Sweden
- 2022
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Ingår i: Lancet Psychiatry. - 2215-0374. ; 9:6, s. 447-457
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Tidskriftsartikel (refereegranskat)abstract
- Background Lithium is the most effective treatment for bipolar disorder, resulting in strong suicide prevention effects. The therapeutic range of lithium, however, is narrow and treatment initiation requires individual titration to address inter-individual variability. We aimed to improve lithium dose prediction using clinical and genomic data. Methods We performed a population pharmacokinetic study followed by a genome-wide association study (GWAS), including two clinical Swedish cohorts. Participants in cohort 1 were from specialised outpatient clinics at Huddinge Hospital, in Stockholm, Sweden, and participants in cohort 2 were identified using the Swedish National Quality Registry for Bipolar disorder (BipolaR). Patients who received a lithium dose corresponding to at least one tablet of lithium sulphate (6 mmol) per day and had clinically relevant plasma concentrations of lithium were included in the study. Data on age, sex, bodyweight, height, creatinine concentration, estimated glomerular filtration rate (eGFR), lithium preparation, number of tablets of lithium per day, serum lithium concentration, and medications affecting kidney function (C09 antihypertensives, C03 [except C03D] sodium-retaining diuretics, and non-steroidal anti-inflammatory drugs) were obtained retrospectively for several timepoints when possible from electronic health records, BipolaR, and the Swedish prescription registry. The median time between timepoints was 1.07 years for cohort 1 and 1.09 years for cohort 2. The primary outcome of interest was the natural logarithm of total body clearance for lithium (CLLi) associated with the clinical variables. The residual effects after accounting for age and sex, representing the individual-level effects (CLLi,age/sex), were used as the dependent variable in a GWAS. Findings 2357 patients who were administered lithium (1423 women [60.4%] and 934 men [39.6%]; mean age 53.6 years [range 17-89], mainly of European descent) were included and 5627 data points were obtained. Age (variance explained [R-2]: R-cohort1(2)=0.41 and R-cohort2(2)=0.31; both p<0.0001), sex (R-cohort1(2)=0.0063 [p=0.045] and R-cohort2(2)=0.026 [p<0.0001]), eGFR (R-cohort1(2)=0.38 and R-cohort2(2)=0.0; both p<0.0001), comedication with diuretics (R-cohort1(2)=0.0058 [p=0.014] and R-cohort2(2)=0.0026 [p<0.0001]), and agents acting on the renin-aldosterone-angiotensin system (R-cohort1(2)=0.028 and R-cohort2(2)=0.015; both p<0.0001) were clinical predictors of CLLi. Notably, an association between CLLi and serum lithium was observed, with a lower CLLi being associated with higher serum lithium (R-cohort1(2)=0.13 and R-cohort2(2)=0.15; both p<0.0001). In a GWAS of CLLi,age/sex, one locus was associated with a change in CLLi (rs583503; beta=-0.053 [95% CI -0.071 to -0.034]; p<0.00000005). We also found enrichment of the associations with genes expressed in the medulla (p=0.0014, corrected FDR=0.04) and cortex of the kidney (p=0.0015, corrected FDR=0.04), as well as associations with polygenic risk scores for eGFR (p value threshold: 0.05, p=0.01), body-mass index (p value threshold: 0.05, p=0.00025), and blood urea nitrogen (p value threshold: 0.001, p=0.00043). The model based on six clinical predictors explained 61.4% of the variance in CLLi in cohort 1 and 49.8% in cohort 2. Adding genetic markers did not lead to major improvement of the models: within the subsample of genotyped individuals, the variance explained only increased from 59.32% to 59.36% in cohort 1 and from 49.21% to 50.03% in cohort 2 when including rs583503 and the four first principal components. Interpretation Our model predictors could be used clinically to better guide lithium dosage, shortening the time to reach therapeutic concentrations, thus improving care. Identification of the first genomic locus and PRS to be associated with CLLi introduces the opportunity of individualised medicine in lithium treatment. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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| 33. |
- White, Christopher J., et al.
(författare)
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SLOW-SPEED SUPERNOVAE FROM THE PALOMAR TRANSIENT FACTORY : TWO CHANNELS
- 2015
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 799:1
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Tidskriftsartikel (refereegranskat)abstract
- Since the discovery of the unusual prototype SN 2002cx, the eponymous class of Type I (hydrogen-poor) supernovae with low ejecta speeds has grown to include approximately two dozen members identified from several heterogeneous surveys, in some cases ambiguously. Here we present the results of a systematic study of 1077 Type I supernovae discovered by the Palomar Transient Factory, leading to nine new members of this peculiar class. Moreover, we find there are two distinct subclasses based on their spectroscopic, photometric, and host galaxy properties: SN 2002cx-like supernovae tend to be in later-type or more irregular hosts, have more varied and generally dimmer luminosities, have longer rise times, and lack a Ti II trough when compared to SN 2002es-like supernovae. None of our objects show helium, and we counter a previous claim of two such events. We also find that the occurrence rate of these transients relative to Type Ia supernovae is 5.6(-3.8)(+22) % (90% confidence), lower compared to earlier estimates. Combining our objects with the literature sample, we propose that these subclasses have two distinct physical origins.
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| 34. |
- Campbell, B, et al.
(författare)
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The effects of growing up on a farm on adult lung function and allergic phenotypes : an international population-based study
- 2017
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 72:3, s. 236-244
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Evidence has suggested that exposure to environmental or microbial biodiversity in early life may impact subsequent lung function and allergic disease risk.OBJECTIVES: To investigate the influence of childhood living environment and biodiversity indicators on atopy, asthma and lung function in adulthood.METHODS AND MEASUREMENTS: The European Community Respiratory Health Survey II investigated ∼10 201 participants aged 26-54 years from 14 countries, including participants' place of upbringing (farm, rural environment or inner city) before age 5 years. A 'biodiversity score' was created based on childhood exposure to cats, dogs, day care, bedroom sharing and older siblings. Associations with lung function, bronchial hyper-responsiveness (BHR), allergic sensitisation, asthma and rhinitis were analysed.MAIN RESULTS: As compared with a city upbringing, those with early-life farm exposure had less atopic sensitisation (adjusted OR 0.46, 95% CI 0.37 to 0.58), atopic BHR (0.54 (0.35 to 0.83)), atopic asthma (0.47 (0.28 to 0.81)) and atopic rhinitis (0.43 (0.32 to 0.57)), but not non-atopic outcomes. Less pronounced protective effects were observed for rural environment exposures. Women with a farm upbringing had higher FEV1 (adjusted difference 110 mL (64 to 157)), independent of sensitisation and asthma. In an inner city environment, a higher biodiversity score was related to less allergic sensitisation.CONCLUSIONS: This is the first study to report beneficial effects of growing up on a farm on adult FEV1. Our study confirmed the beneficial effects of early farm life on sensitisation, asthma and rhinitis, and found a similar association for BHR. In persons with an urban upbringing, a higher biodiversity score predicted less allergic sensitisation, but to a lesser magnitude than a childhood farm environment.
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| 35. |
- Davis, Tamara, et al.
(författare)
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Scrutinizing Exotic Cosmological Models Using ESSENCE Supernova Data Combined with Other Cosmological Probes
- 2007
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Ingår i: The Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 666:2, s. 716-725
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Tidskriftsartikel (refereegranskat)abstract
- The first cosmological results from the ESSENCE supernova survey (Wood-Vasey and coworkers) are extended to a wider range of cosmological models including dynamical dark energy and nonstandard cosmological models. We fold in a greater number of external data sets such as the recent Higher-z release of high-redshift supernovae (Riess and coworkers), as well as several complementary cosmological probes. Model comparison statistics such as the Bayesian and Akaike information criteria are applied to gauge the worth of models. These statistics favor models that give a good fit with fewer parameters. Based on this analysis, the preferred cosmological model is the flat cosmological constant model, where the expansion history of the universe can be adequately described with only one free parameter describing the energy content of the universe. Among the more exotic models that provide good fits to the data, we note a preference for models whose best-fit parameters reduce them to the cosmological constant model.
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| 36. |
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| 37. |
- Kuiper, I. N., et al.
(författare)
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Agreement in reporting of asthma by parents or offspring - the RHINESSA generation study
- 2018
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Ingår i: Bmc Pulmonary Medicine. - : Springer Science and Business Media LLC. - 1471-2466. ; 18:122
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Tidskriftsartikel (refereegranskat)abstract
- Background: Self-report questionnaires are commonly used in epidemiology, but may be susceptible to misclassification, especially if answers are given on behalf of others, e.g. children or parents. The aim was to determine agreement and analyse predictors of disagreement in parents' reports of offspring asthma, and in offspring reports of parents' asthma. Methods: In the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study, 6752 offspring (age range 18-51 years) and their parents (age range 39-66 years) reported their own and each other's asthma status. Agreement between asthma reports from offspring and parents was determined by calculating sensitivity, specificity, positive and negative predictive value and Cohen's kappa. The participants' own answers regarding themselves were defined as the gold standard. To investigate predictors for disagreement logistic regression analyses were performed to obtain odds ratios (OR) with 95% confidence intervals (CI) for sex, smoking status, education, comorbidity and severity of asthma. Results: Agreement was good for parental report of offspring early onset asthma (< 10 years, Cohen's kappa 0.72) and moderate for offspring later onset asthma (Cohen's kappa 0.46). Specificity was 0.99 for both, and sensitivity was 0.68 and 0.36, respectively. For offspring report of maternal and paternal asthma the agreement was good (Cohen's kappa 0.69 and 0.68), specificity was 0.96 and 0.97, and sensitivity was 0.72 and 0.68, respectively. The positive predictive value (PPV) was lowest for offspring report of maternal asthma (0.75), and highest for parents' report of early onset asthma in the offspring (0.83). The negative predictive value (NPV) was high for all four groups (0.94-0.97). In multivariate analyses current smokers (OR = 1.46 [95% CI 1.05, 2.02]) and fathers (OR = 1.31 [95% CI 1. 08, 1.59]) were more likely to report offspring asthma incorrectly. Offspring wheeze was associated with reporting parental asthma incorrectly (OR = 1.60 [95% CI 1.21, 2.11]), both under- and over reporting. Conclusions: Asthma reports across generations show moderate to good agreement, making information from other generations a useful tool in the absence of direct reports.
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| 38. |
- Matheson, M., et al.
(författare)
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The effects of road traffic and aircraft noise exposure on children’s episodic memory : The RANCH Project
- 2010
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Ingår i: Noise & Health. - : Medknow. - 1463-1741 .- 1998-4030. ; 12:49, s. 244-254
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have found that chronic exposure to aircraft noise has a negative effect on children's performance on tests of episodic memory. The present study extended the design of earlier studies in three ways: firstly, by examining the effects of two noise sources, aircraft and road traffic, secondly, by examining exposure-effect relationships, and thirdly, by carrying out parallel field studies in three European countries, allowing cross-country comparisons to be made. A total of 2844 children aged between 8 years 10 months and 12 years 10 months (mean age 10 years 6 months) completed classroom-based tests of cued recall, recognition memory and prospective memory. Questionnaires were also completed by the children and their parents in order to provide information about socioeconomic context. Multilevel modeling analysis revealed aircraft noise to be associated with an impairment of recognition memory in a linear exposure-effect relationship. The analysis also found road traffic noise to be associated with improved performance on cued recall in a linear exposure-effect relationship. No significant association was found between exposure to aircraft noise and cued recall or prospective memory. Likewise, no significant association was found between road traffic noise and recognition or prospective memory. Taken together, these findings indicate that exposure to aircraft noise and road traffic noise can impact on certain aspects of children's episodic memory.
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| 39. |
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| 40. |
- Rest, A., et al.
(författare)
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DIRECT CONFIRMATION OF THE ASYMMETRY OF THE CAS A SUPERNOVA WITH LIGHT ECHOES
- 2011
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 732:1, s. 3-
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Tidskriftsartikel (refereegranskat)abstract
- We report the first detection of asymmetry in a supernova (SN) photosphere based on SN light echo (LE) spectra of Cas A from the different perspectives of dust concentrations on its LE ellipsoid. New LEs are reported based on difference images, and optical spectra of these LEs are analyzed and compared. After properly accounting for the effects of finite dust-filament extent and inclination, we find one field where the He I lambda 5876 and Ha features are blueshifted by an additional similar to 4000 km s(-1) relative to other spectra and to the spectra of the Type IIb SN 1993J. That same direction does not show any shift relative to other Cas A LE spectra in the Ca II near-infrared triplet feature. We compare the perspectives of the Cas A LE dust concentrations with recent three-dimensional modeling of the SN remnant (SNR) and note that the location having the blueshifted He I and Ha features is roughly in the direction of an Fe-rich outflow and in the opposite direction of the motion of the compact object at the center of the SNR. We conclude that Cas A was an intrinsically asymmetric SN. Future LE spectroscopy of this object, and of other historical SNe, will provide additional insight into the connection of the explosion mechanism to SN then to SNR, as well as give crucial observational evidence regarding how stars explode.
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