| 1. |
- Niemi, MEK, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
|
|
| 3. |
- Le Clerc, S., et al.
(författare)
-
HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
- 2021
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 x 10(-3); FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
|
|
| 4. |
- Amare, A. T., et al.
(författare)
-
Association of polygenic score for major depression with response to lithium in patients with bipolar disorder
- 2021
-
Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 2457-2470
-
Tidskriftsartikel (refereegranskat)abstract
- Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi(+)Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18-2.01) and European sample: OR = 1.75 (95% CI: 1.30-2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61-4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.
|
|
| 5. |
- Cearns, M., et al.
(författare)
-
Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach
- 2022
-
Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 220:4, s. 219-228
-
Tidskriftsartikel (refereegranskat)abstract
- Background Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment. Aims To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder. Method This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi(+)Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework. Results The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data. Conclusions Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
|
|
| 6. |
- Deka, P. P., et al.
(författare)
-
The MeerKAT Absorption Line Survey (MALS) Data Release. I. Stokes I Image Catalogs at 1-1.4 GHz
- 2024
-
Ingår i: Astrophysical Journal, Supplement Series. - 1538-4365 .- 0067-0049. ; 270:2
-
Tidskriftsartikel (refereegranskat)abstract
- The MeerKAT Absorption Line Survey (MALS) has observed 391 telescope pointings at the L band (900-1670 MHz) at delta less than or similar to +20 degrees. We present radio continuum images and a catalog of 495,325 (240,321) radio sources detected at a signal-to-noise ratio (S/N) > 5 over an area of 2289 deg(2) (1132 deg(2)) at 1006 MHz (1381 MHz). Every MALS pointing contains a central bright radio source (S 1 GHz greater than or similar to 0.2 Jy). The median spatial resolution is 12 ''(8 ''). The median rms noise away from the pointing center is 25 mu Jy beam(-1) (22 mu Jy beam-1) and is within similar to 15% of the achievable theoretical sensitivity. The flux density scale ratio and astrometric accuracy deduced from multiply observed sources in MALS are <1% (8% scatter) and 1 '', respectively. Through comparisons with NVSS and FIRST at 1.4 GHz, we establish the catalog's accuracy in the flux density scale and astrometry to be better than 6% (15% scatter) and 0.'' 8, respectively. The median flux density offset is higher (9%) for an alternate beam model based on holographic measurements. The MALS radio source counts at 1.4 GHz are in agreement with literature. We estimate spectral indices (alpha) of a subset of 125,621 sources (S/N > 8), confirm the flattening of spectral indices with decreasing flux density, and identify 140 ultra-steep-spectrum (alpha < -1.3) sources as prospective high-z radio galaxies (z > 2). We have identified 1308 variable and 122 transient radio sources comprising primarily active galactic nuclei that demonstrate long-term (26 yr) variability in their observed flux densities. The MALS catalogs and images are publicly available at https://mals.iucaa.in.
|
|
| 7. |
- Gunduz, C., et al.
(författare)
-
Hyperlipidaemia prevalence and cholesterol control in obstructive sleep apnoea: Data from the European sleep apnea database (ESADA)
- 2019
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 676-688
-
Tidskriftsartikel (refereegranskat)abstract
- Background and objective Obstructive sleep apnoea (OSA) and hyperlipidaemia are independent risk factors for cardiovascular disease. This study investigates the association between OSA and prevalence of hyperlipidaemia in patients of the European Sleep Apnea Database (ESADA) cohort. Methods The cross-sectional analysis included 11 892 patients (age 51.9 +/- 12.5 years, 70% male, body mass index (BMI) 31.3 +/- 6.6 kg/m(2), mean oxygen desaturation index (ODI) 23.7 +/- 25.5 events/h) investigated for OSA. The independent odds ratio (OR) for hyperlipidaemia in relation to measures of OSA (ODI, apnoea-hypopnoea index, mean and lowest oxygen saturation) was determined by means of general linear model analysis with adjustment for important confounders such as age, BMI, comorbidities and study site. Results Hyperlipidaemia prevalence increased from 15.1% in subjects without OSA to 26.1% in those with severe OSA, P < 0.001. Corresponding numbers in patients with diabetes were 8.5% and 41.5%, P < 0.001. Compared with ODI quartile I, patients in ODI quartiles II-IV had an adjusted OR (95% CI) of 1.33 (1.15-1.55), 1.37 (1.17-1.61) and 1.33 (1.12-1.58) (P < 0.001), respectively, for hyperlipidaemia. Obesity was defined as a significant risk factor for hyperlipidaemia. Subgroups of OSA patients with cardio-metabolic comorbidities demonstrated higher prevalence of HL. In addition, differences in hyperlipidaemia prevalence were reported in European geographical regions with the highest prevalence in Central Europe. Conclusion Obstructive sleep apnoea, in particular intermittent hypoxia, was independently associated with the prevalence of hyperlipidaemia diagnosis.
|
|
| 8. |
- Gunduz, C., et al.
(författare)
-
Long-term positive airway pressure therapy is associated with reduced total cholesterol levels in patients with obstructive sleep apnea: data from the European Sleep Apnea Database (ESADA)
- 2020
-
Ingår i: Sleep Medicine. - : Elsevier BV. - 1389-9457. ; 75, s. 201-209
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aim: Obstructive sleep apnea (OSA) is an independent risk factor for dyslipidemia. The current study examined the effects of positive airway pressure (PAP) treatment on lipid status in the European Sleep Apnea Database (ESADA). Methods: The prospective cohort study enrolled 1564 OSA subjects (74% male, mean age 54 ± 11y, body mass index (BMI) 32.7 ± 6.6 kg/m2 and apnea-hypopnea index (AHI) 40.3 ± 24.4 n/h) undergoing PAP therapy for at least three months (mean 377.6 ± 419.5 days). Baseline and follow-up total cholesterol (TC) from nine centers were analyzed. Repeated measures and logistic regression tests (adjusted for age, sex, weight changes, lipid lowering medication, PAP compliance, and treatment duration) were used to compare changes in TC concentration. Incident risk for a coronary heart disease event (CHD) was used to compute a Framingham CHD risk score (estimated from age, BMI, blood pressure, and TC). Results: Adjusted means of TC decreased from 194.2 mg/dl to 189.3 mg/dl during follow-up (p = 0.019). A clinically significant (10%) reduction of TC at PAP follow-up was observed in 422 patients (27%). Duration of PAP therapy was identified as independent predictor for TC reduction, which implies an approximately 10% risk reduction for incident CHD events (from 26.7% to 24.1% in men and from 11.2% to 10.1% in women, p < 0.001 respectively). Conclusion: This observational study demonstrates a reduction of TC after long-term PAP treatment. The close association between TC concentration and cardiovascular (CV) mortality suggests that identification and treatment of OSA may have a beneficial effect on overall CV risk due to this mechanism. This possibility needs to be evaluated in prospective randomized studies. © 2020 Elsevier B.V.
|
|
| 9. |
- Zerbi, F. M., et al.
(författare)
-
HIRES : The High Resolution Spectrograph for E-ELT
- 2014
-
Ingår i: Ground-based and Airborne Instrumentation for Astronomy V. - : SPIE. - 9780819496157
-
Konferensbidrag (refereegranskat)abstract
- The current instrumentation plan for the E-ELT foresees a High Resolution Spectrograph conventionally indicated as HIRES. Shaped on the study of extra-solar planet atmospheres, Pop-III stars and fundamental physical constants, HIRES is intended to embed observing modes at high-resolution (up to R=150000) and large spectral range (from the blue limit to the K band) useful for a large suite of science cases that can exclusively be tackled by the E-ELT. We present in this paper the solution for HIRES envisaged by the "HIRES initiative", the international collaboration established in 2013 to pursue a HIRES on E-ELT.
|
|
| 10. |
- Combes, F., et al.
(författare)
-
PKS 1830-211: OH and HI at z = 0.89 and the first MeerKAT UHF spectrum
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 648
-
Tidskriftsartikel (refereegranskat)abstract
- The Large Survey Project (LSP) "MeerKAT Absorption Line Survey"(MALS) is a blind H I 21 cm and OH 18 cm absorption line survey in the L- and UHF-bands, primarily designed to better determine the occurrence of atomic and molecular gas in the circumgalactic and intergalactic medium, and its redshift evolution. Here we present the first results using the UHF band obtained towards the strongly lensed radio source PKS 1830-211, revealing the detection of absorption produced by the lensing galaxy. With merely 90 min of data acquired on-source for science verification and processed using the Automated Radio Telescope Imaging Pipeline (ARTIP), we detect in absorption the known H I 21 cm and OH 18 cm main lines at z = 0.89 at an unprecedented signal-to-noise ratio (4000 in the continuum, in each 6 km s-1 wide channel). For the first time we report the detection of OH satellite lines at z = 0.89, which until now have not been detected at z > 0.25. We decompose the OH lines into a thermal and a stimulated contribution, where the 1612 and 1720 MHz lines are conjugate. The total OH 1720 MHz emission line luminosity is 6100 L⊙. This is the most luminous known 1720 MHz maser line and is also among the most luminous of the OH main line megamasers. The absorption components of the different images of the background source sample different light paths in the lensing galaxy, and their weights in the total absorption spectrum are expected to vary in time on daily and monthly time scales. We compare our normalized spectra with those obtained more than 20 years ago, and find no variation. We interpret the absorption spectra with the help of a lens galaxy model derived from an N-body hydrodynamical simulation, with a morphology similar to its optical HST image. The resulting absorption lines depend mainly on the background continuum and the radial distribution of the gas surface density for each atomic and molecular species. We show that it is possible to reproduce the observations assuming a realistic spiral galaxy disk without invoking any central gas outflows. However, there are distinct and faint high-velocity features in the ALMA millimeter absorption spectra that most likely originate from high-velocity clouds or tidal features. These clouds may contribute to broaden the H I and OH spectra.
|
|
