| 1. |
- Le Clerc, S., et al.
(author)
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HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
- 2021
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)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.
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| 2. |
- Meech, K. J., et al.
(author)
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EPOXI: Comet 103P/Hartley 2 Observations from a Worldwide Campaign
- 2011
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In: Astrophysical Journal Letters. - London : IOP. - 2041-8213 .- 2041-8205. ; 734:L1, s. 1-9
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Journal article (peer-reviewed)abstract
- Earth- and space-based observations provide synergistic information for space mission encounters by providing data over longer timescales, at different wavelengths and using techniques that are impossible with an in situ flyby. We report here such observations in support of the EPOXI spacecraft flyby of comet 103P/Hartley 2. The nucleus is small and dark, and exhibited a very rapidly changing rotation period. Prior to the onset of activity, the period was ~16.4?hr. Starting in 2010 August the period changed from 16.6?hr to near 19?hr in December. With respect to dust composition, most volatiles and carbon and nitrogen isotope ratios, the comet is similar to other Jupiter-family comets. What is unusual is the dominance of CO 2 -driven activity near perihelion, which likely persists out to aphelion. Near perihelion the comet nucleus was surrounded by a large halo of water-ice grains that contributed significantly to the total water production.
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| 3. |
- Reinbold, C. S., et al.
(author)
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Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder
- 2018
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In: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 9
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Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen) Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD associated miRNAs However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted.
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| 4. |
- Schubert, K. O., et al.
(author)
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Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients
- 2021
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Journal article (peer-reviewed)abstract
- Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi(+)Gen; ). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.
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| 5. |
- Abramowski, A., et al.
(author)
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A multiwavelength view of the flaring state of PKS 2155-304 in 2006
- 2012
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 539, s. A149-
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Journal article (peer-reviewed)abstract
- Context. Multiwavelength (MWL) observations of the blazar PKS 2155-304 during two weeks in July and August 2006, the period when two exceptional flares at very high energies (VHE, E greater than or similar to 100 GeV) occurred, provide a detailed picture of the evolution of its emission. The complete data set from this campaign is presented, including observations in VHE gamma-rays (H.E.S. S.), X-rays (RXTE, Chandra, Swift XRT), optical (Swift UVOT, Bronberg, Watcher, ROTSE), and in the radio band (NRT, HartRAO, ATCA). Optical and radio light curves from 2004 to 2008 are compared to the available VHE data from this period, to put the 2006 campaign into the context of the long-term evolution of the source. Aims. The data set offers a close view of the evolution of the source on different time scales and yields new insights into the properties of the emission process. The predictions of synchrotron self-Compton (SSC) scenarios are compared to the MWL data, with the aim of describing the dominant features in the data down to the hour time scale. Methods. The spectral variability in the X-ray and VHE bands is explored and correlations between the integral fluxes at different wavelengths are evaluated. SSC modelling is used to interpret the general trends of the varying spectral energy distribution. Results. The X-ray and VHE gamma-ray emission are correlated during the observed high state of the source, but show no direct connection with longer wavelengths. The long-term flux evolution in the optical and radio bands is found to be correlated and shows that the source reaches a high state at long wavelengths after the occurrence of the VHE flares. Spectral hardening is seen in the Swift XRT data. Conclusions. The nightly averaged high-energy spectra of the non-flaring nights can be reproduced by a stationary one-zone SSC model, with only small variations in the parameters. The spectral and flux evolution in the high-energy band during the night of the second VHE flare is modelled with multi-zone SSC models, which can provide relatively simple interpretations for the hour time-scale evolution of the high-energy emission, even for such a complex data set. For the first time in this type of source, a clear indication is found for a relation between high activity at high energies and a long-term increase in the low frequency fluxes.
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| 6. |
- Amare, A. T., et al.
(author)
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Association of polygenic score for major depression with response to lithium in patients with bipolar disorder
- 2021
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 2457-2470
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Journal article (peer-reviewed)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.
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| 7. |
- Cearns, M., et al.
(author)
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Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach
- 2022
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In: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 220:4, s. 219-228
-
Journal article (peer-reviewed)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.
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| 8. |
- Abramowski, A., et al.
(author)
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HESS J1943+213 : a candidate extreme BL Lacertae object
- 2011
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 529, s. A49-
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Journal article (peer-reviewed)abstract
- Context. The H. E. S. S. Cherenkov telescope array has been surveying the Galactic plane for new VHE (>100 GeV) gamma-ray sources. Aims. We report on a newly detected point-like source, HESS J1943+213. This source coincides with an unidentified hard X-ray source IGR J19443+2117, which was proposed to have radio and infrared counterparts. Methods. We combine new H. E. S. S., Fermi/LAT and Nancay Radio Telescope observations with pre-existing non-simultaneous multi-wavelength observations of IGR J19443+2117 and discuss the likely source associations as well as the interpretation as an active galactic nucleus, a gamma-ray binary or a pulsar wind nebula. Results. HESS J1943+213 is detected at the significance level of 7.9 sigma (post-trials) at RA(J2000) = 19(h)43(m)55(s) +/- 1(stat)(s) +/- 1(sys)(s), Dec(J2000) = +21 degrees 18'8 '' +/- 17(stat)'' +/- 20(sys)''. The source has a soft spectrum with photon index Gamma = 3.1 +/- 0.3(stat) +/- 0.2(sys) and a flux above 470 GeV of (1.3 +/- 0.2(stat) +/- 0.3(sys)) x 10(-12) cm(-2) s(-1). There is no Fermi/LAT counterpart down to a flux limit of 6 x 10(-9) cm(-2) s(-1) in the 0.1-100 GeV energy range (95% confidence upper limit calculated for an assumed power-law model with a photon index Gamma = 2.0). The data from radio to VHE gamma-rays do not show any significant variability. Conclusions. The lack of a massive stellar counterpart disfavors the binary hypothesis, while the soft VHE spectrum would be very unusual in case of a pulsar wind nebula. In addition, the distance estimates for Galactic counterparts places them outside of the Milky Way. All available observations favor an interpretation as an extreme, high-frequency peaked BL Lac object with a redshift z > 0.14. This would be the first time a blazar is detected serendipitously from ground-based VHE observations, and the first VHE AGN detected in the Galactic Plane.
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| 9. |
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| 10. |
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| 11. |
- Scott, J., et al.
(author)
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Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative
- 2019
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In: International Journal of Bipolar Disorders. - : Springer Science and Business Media LLC. - 2194-7511. ; 7:1
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Journal article (peer-reviewed)abstract
- Background Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need. Structure The H2020-funded Response to Lithium Network (R-LiNK; ) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants' response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence. Conclusions The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment.
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| 12. |
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| 13. |
- Anderson, P., et al.
(author)
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Improving the delivery of brief interventions for heavy drinking in primary health care: outcome results of the Optimizing Delivery of Health Care Intervention (ODHIN) five-country cluster randomized factorial trial
- 2016
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In: Addiction. - : Wiley. - 1360-0443 .- 0965-2140. ; 111:11, s. 1935-1945
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Journal article (peer-reviewed)abstract
- Aim: To test if training and support, financial reimbursement and option of referring screen-positive patients to an internet-based method of giving advice (eBI) can increase primary health-care providers' delivery of Alcohol Use Disorders Identification Test (AUDIT)-C-based screening and advice to heavy drinkers. Design: Cluster randomized factorial trial with 12-week implementation and measurement period. Setting: Primary health-care units (PHCU) in different locations throughout Catalonia, England, the Netherlands, Poland and Sweden. Participants: A total of 120 PHCU, 24 in each of Catalonia, England, the Netherlands, Poland and Sweden. Interventions: PHCUs were randomized to one of eight groups: care as usual, training and support (TS), financial reimbursement (FR) and eBI; paired combinations of TS, FR and eBI, and all of FR, TS and eBI. Measurements: The primary outcome measure was the proportion of eligible adult (age 18+ years) patients screened during a 12-week implementation period. Secondary outcome measures were proportion of screen-positive patients advised; and proportion of consulting adult patients given an intervention (screening and advice to screen-positives) during the same 12-week implementation period. Findings: During a 4-week baseline measurement period, the proportion of consulting adult patients who were screened for their alcohol consumption was 0.059 per PHCU (95% CI 0.034 to 0.084). Based on the factorial design, the ratio of the logged proportion screened during the 12-week implementation period was 1.48 (95% CI=1.13–1.95) in PHCU that received TS versus PHCU that did not receive TS; for FR, the ratio was 2.00 (95% CI=1.56–2.56). The option of referral to eBI did not lead to a higher proportion of patients screened. The ratio for TS plus FR was 2.34 (95% CI=1.77–3.10), and the ratio for TS plus FR plus eBI was1.68 (95% CI=1.11–2.53). Conclusions: Providing primary health-care units with training, support and financial reimbursement for delivering Alcohol Use Disorders Identification Test-C-based screening and advice to heavy drinkers increases screening for alcohol consumption. Providing primary health-care units with the option of referring screen-positive patients to an internet-based method of giving advice does not appear to increase screening for alcohol consumption. © 2016 Society for the Study of Addiction
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| 14. |
- Bendtsen, Preben, et al.
(author)
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Professional's Attitudes Do Not Influence Screening and Brief Interventions Rates for Hazardous and Harmful Drinkers: Results from ODHIN Study
- 2015
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In: Alcohol and Alcoholism. - : Oxford University Press (OUP). - 0735-0414 .- 1464-3502. ; 50:4, s. 430-437
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Journal article (peer-reviewed)abstract
- To determine the relation between existing levels of alcohol screening and brief intervention rates in five European jurisdictions and role security and therapeutic commitment by the participating primary healthcare professionals. Health care professionals consisting of, 409 GPs, 282 nurses and 55 other staff including psychologists, social workers and nurse aids from 120 primary health care centres participated in a cross-sectional 4-week survey. The participants registered all screening and brief intervention activities as part of their normal routine. The participants also completed the Shortened Alcohol and Alcohol Problems Perception Questionnaire (SAAPPQ), which measure role security and therapeutic commitment. The only significant but small relationship was found between role security and screening rate in a multilevel logistic regression analysis adjusted for occupation of the provider, number of eligible patients and the random effects of jurisdictions and primary health care units (PHCU). No significant relationship was found between role security and brief intervention rate nor between therapeutic commitment and screening rate/brief intervention rate. The proportion of patients screened varied across jurisdictions between 2 and 10%. The findings show that the studied factors (role security and therapeutic commitment) are not of great importance for alcohol screening and BI rates. Given the fact that screening and brief intervention implementation rate has not changed much in the last decade in spite of increased policy emphasis, training initiatives and more research being published, this raises a question about what else is needed to enhance implementation.
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| 15. |
- Keurhorst, M., et al.
(author)
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Impact of primary healthcare providers' initial role security and therapeutic commitment on implementing brief interventions in managing risky alcohol consumption: a cluster randomised factorial trial
- 2016
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In: Implementation Science. - : Springer Science and Business Media LLC. - 1748-5908. ; 11
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Journal article (peer-reviewed)abstract
- Background: Brief interventions in primary healthcare are cost-effective in reducing drinking problems but poorly implemented in routine practice. Although evidence about implementing brief interventions is growing, knowledge is limited with regard to impact of initial role security and therapeutic commitment on brief intervention implementation. Methods: In a cluster randomised factorial trial, 120 primary healthcare units (PHCUs) were randomised to eight groups: care as usual, training and support, financial reimbursement, and the opportunity to refer patients to an internet-based brief intervention (e-BI); paired combinations of these three strategies, and all three strategies combined. To explore the impact of initial role security and therapeutic commitment on implementing brief interventions, we performed multilevel linear regression analyses adapted to the factorial design. Results: Data from 746 providers from 120 PHCUs were included in the analyses. Baseline role security and therapeutic commitment were found not to influence implementation of brief interventions. Furthermore, there were no significant interactions between these characteristics and allocated implementation groups. Conclusions: The extent to which providers changed their brief intervention delivery following experience of different implementation strategies was not determined by their initial attitudes towards alcohol problems. In future research, more attention is needed to unravel the causal relation between practitioners' attitudes, their actual behaviour and care improvement strategies to enhance implementation science.
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| 16. |
- Pilla, Rachel M., et al.
(author)
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Global data set of long-term summertime vertical temperature profiles in 153 lakes
- 2021
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In: Scientific Data. - : Springer Nature. - 2052-4463. ; 8:1
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Journal article (peer-reviewed)abstract
- Climate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change.
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| 17. |
- Biver, N, et al.
(author)
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Long-term evolution of the outgassing of comet Hale-Bopp from radio observations
- 1997
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In: EARTH MOON AND PLANETS. - : KLUWER ACADEMIC PUBL. - 0167-9295. ; 78:1-3, s. 5-11
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Journal article (peer-reviewed)abstract
- C/1995 O1 (Hale-Bopp) has been observed on a regular basis since August 1995 at millimetre and submillimetre wavelengths using IRAM, JCMT, CSO and SEST radio telescopes. The production rates of eight molecular species (CO, HCN, CH3OH, H2CO, H2S, CS, CH3CN
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| 18. |
- Palacio-Vieira, J., et al.
(author)
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Improving screening and brief intervention activities in primary health care: Secondary analysis of professional accuracy based on the AUDIT-C
- 2018
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In: Journal of Evaluation In Clinical Practice. - : WILEY. - 1356-1294 .- 1365-2753. ; 24:2, s. 369-374
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Journal article (peer-reviewed)abstract
- Introduction and objectiveThe ODHIN trial found that training and support and financial reimbursement increased the proportion of patients that were screened and given advice for their heavy drinking in primary health care. However, the impact of these strategies on professional accuracy in delivering screening and brief advice is underresearched and is the focus of this paper. MethodFrom 120 primary health care units (24 in each jurisdiction: Catalonia, England, the Netherlands, Poland, and Sweden), 746 providers participated in the baseline and the 12-week implementation periods. Accuracy was measured in 2 ways: correctness in completing and scoring the screening instrument, AUDIT-C; the proportion of screen-negative patients given advice, and the proportion of screen-positive patients not given advice. Odds ratios of accuracy were calculated for type of profession and for intervention group: training and support, financial reimbursement, and internet-based counselling. ResultsThirty-two of 36711 questionnaires were incorrectly completed, and 65 of 29641 screen-negative patients were falsely classified. At baseline, 27% of screen-negative patients were given advice, and 22.5% screen-positive patients were not given advice. These proportions halved during the 12-week implementation period, unaffected by training. Financial reimbursement reduced the proportion of screen-positive patients not given advice (OR=0.56; 95% CI, 0.31-0.99; Pamp;lt;.05). ConclusionAlthough the use of AUDIT-C as a screening tool was accurate, a considerable proportion of risky drinkers did not receive advice, which was reduced with financial incentives.
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| 19. |
- Pilla, Rachel M., et al.
(author)
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Deeper waters are changing less consistently than surface waters in a global analysis of 102 lakes
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Globally, lake surface water temperatures have warmed rapidly relative to air temperatures, but changes in deepwater temperatures and vertical thermal structure are still largely unknown. We have compiled the most comprehensive data set to date of long-term (1970–2009) summertime vertical temperature profiles in lakes across the world to examine trends and drivers of whole-lake vertical thermal structure. We found significant increases in surface water temperatures across lakes at an average rate of + 0.37 °C decade−1, comparable to changes reported previously for other lakes, and similarly consistent trends of increasing water column stability (+ 0.08 kg m−3 decade−1). In contrast, however, deepwater temperature trends showed little change on average (+ 0.06 °C decade−1), but had high variability across lakes, with trends in individual lakes ranging from − 0.68 °C decade−1 to + 0.65 °C decade−1. The variability in deepwater temperature trends was not explained by trends in either surface water temperatures or thermal stability within lakes, and only 8.4% was explained by lake thermal region or local lake characteristics in a random forest analysis. These findings suggest that external drivers beyond our tested lake characteristics are important in explaining long-term trends in thermal structure, such as local to regional climate patterns or additional external anthropogenic influences.
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| 20. |
- Amare, Azmeraw T, et al.
(author)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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In: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Journal article (peer-reviewed)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 21. |
- Amare, Azmeraw T, et al.
(author)
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Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
- 2018
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In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74
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Journal article (peer-reviewed)abstract
- Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
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| 22. |
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| 23. |
- Biver, N., et al.
(author)
-
Isotopic ratios of H, C, N, O, and S in comets C/2012 F6 (Lemmon) and C/2014 Q2 (Lovejoy)
- 2016
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 589, s. Art. no. A78-
-
Journal article (peer-reviewed)abstract
- The apparition of bright comets C/2012 F6 (Lemmon) and C/2014 Q2 (Lovejoy) in March-April 2013 and January 2015, combined with the improved observational capabilities of submillimeter facilities, offered an opportunity to carry out sensitive compositional and isotopic studies of the volatiles in their coma. We observed comet Lovejoy with the IRAM 30 m telescope between 13 and 26 January 2015, and with the Odin submillimeter space observatory on 29 January-3 February 2015. We detected 22 molecules and several isotopologues. The (H2O)-O-16 and (H2O)-O-18 production rates measured with Odin follow a periodic pattern with a period of 0.94 days and an amplitude of similar to 25%. The inferred isotope ratios in comet Lovejoy are O-16/O-18 = 499 +/- 24 and D/H = 1.4 +/- 0.4 x 10(-4) in water, S-32/S-34 = 24.7 +/- 3.5 in CS, all compatible with terrestrial values. The ratio C-12/C-13 = 109 +/- 14 in HCN is marginally higher than terrestrial and N-14/N-15 = 145 +/- 12 in HCN is half the Earth ratio. Several upper limits for D/H or C-12/C-13 in other molecules are reported. From our observation of HDO in comet C/2014 Q2 (Lovejoy), we report the first D/H ratio in an Oort Cloud comet that is not larger than the terrestrial value. On the other hand, the observation of the same HDO line in the other Oort-cloud comet, C/2012 F6 (Lemmon), suggests a D/H value four times higher. Given the previous measurements of D/H in cometary water, this illustrates that a diversity in the D/H ratio and in the chemical composition, is present even within the same dynamical group of comets, suggesting that current dynamical groups contain comets formed at very different places or times in the early solar system.
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| 24. |
- Biver, N., et al.
(author)
-
Periodic variation in the water production of comet C/2001 Q4 (NEAT) observed with the Odin satellite
- 2009
-
In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 501:1, s. 359-366
-
Journal article (peer-reviewed)abstract
- Context: Comet C/2001 Q4 (NEAT) was extensively studied with the 1.1-m submillimetre telescope of the Odin satellite. The H2O line at 557 GHz was regularly observed from 6 March to 16 May 2004 and nearly continuously monitored during 3 periods between 26 April and 2 May 2004. Aims: This last set of data shows periodic variations in the line intensity, and we looked for characterising the long- and short-term behaviour of this comet. Methods: We used the variance ratio method and χ2 minimization to find the period of variation in the water production rate and simulations to infer its amplitude at the nucleus surface. Results: A 40% periodic variation in the water production rate is measured with a period of 0.816±0.004 day (19.58±0.1 h). The comet also exhibits a seasonal effect with a mean peak of outgassing around 2.7×1029 molec. s-1 taking place about 18 days before perihelion.
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| 25. |
- Biver, N., et al.
(author)
-
Radio observations of Comet 9P/Tempel 1 before and after Deep Impact
- 2007
-
In: Icarus. - : Elsevier BV. - 1090-2643 .- 0019-1035. ; 191:2, s. 494-512
-
Journal article (peer-reviewed)abstract
- Comet 9P/Tempel 1 was the target of a multi-wavelength worldwide investigation in 2005. The NASA Deep Impact mission reached the comet on 4.24 July 2005, delivering a 370-kg impactor which hit the comet at 10.3 km s -1 . Following this impact, a cloud of gas and dust was excavated from the comet nucleus. The comet was observed in 2005 prior to and after the impact, at 18-cm wavelength with the Nançay radio telescope, in the millimeter range with the IRAM and CSO radio telescopes, and at 557 GHz with the Odin satellite. OH observations at Nançay provided a 4-month monitoring of the outgassing of the comet from March to June, followed by the observation of H 2 O with Odin from June to August 2005. The peak of outgassing was found to be around 1 × 10 28 molec. s -1 between May and July. Observations conducted with the IRAM 30-m radio telescope in May and July 2005 resulted in detections of HCN, CH 3 OH and H 2 S with classical abundances relative to water (0.12, 2.7 and 0.5%, respectively). In addition, a variation of the HCN production rate with a period of 1.73 ± 0.10 days was observed in May 2005, consistent with the 1.7-day rotation period of the nucleus. The phase of these variations, as well as those of CN seen in July by Jehin et al. [Jehin, E., Manfroid, J., Hutsemékers, D., Cochran, A.L., Arpigny, C., Jackson, W.M., Rauer, H., Schulz, R., Zucconi, J.-M., 2006. Astrophys. J. 641, L145-L148], is consistent with a rotation period of the nucleus of 1.715 days and a strong variation of the outgassing activity by a factor 3 from minimum to maximum. This also implies that the impact took place on the rising phase of the "natural" outgassing which reached its maximum ≈4 h after the impact. Post-impact observations at IRAM and CSO did not reveal a significant change of the outgassing rates and relative abundances, with the exception of CH 3 OH which may have been more abundant by up to one order of magnitude in the ejecta. Most other variations are linked to the intrinsic variability of the comet. The Odin satellite monitored nearly continuously the H 2 O line at 557 GHz during the 38 h following the impact on the 4th of July, in addition to weekly monitoring. Once the periodic variations related to the nucleus rotation are removed, a small increase of outgassing related to the impact is present, which corresponds to the release of ≈ 5000 ± 2000 tons of water. Two other bursts of activity, also observed at other wavelengths, were seen on 23 June and 7 July; they correspond to even larger releases of gas. © 2006 Elsevier Inc. All rights reserved.
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| 26. |
- Biver, N., et al.
(author)
-
Radio observations of Comet 9P/Tempel 1 before and after Deep Impact
- 2007
-
In: Icarus. - : Elsevier BV. - 1090-2643 .- 0019-1035. ; 187:1, s. 253-271
-
Journal article (peer-reviewed)abstract
- Comet 9P/Tempel 1 was the target of a multi-wavelength worldwide investigation in 2005. The NASA Deep Impact mission reached the comet on 4.24 July 2005, delivering a 370-kg impactor which hit the comet at 10.3 km s -1 . Following this impact, a cloud of gas and dust was excavated from the comet nucleus. The comet was observed in 2005 prior to and after the impact, at 18-cm wavelength with the Nançay radio telescope, in the millimeter range with the IRAM and CSO radio telescopes, and at 557 GHz with the Odin satellite. OH observations at Nançay provided a 4-month monitoring of the outgassing of the comet from March to June, followed by the observation of H 2 O with Odin from June to August 2005. The peak of outgassing was found to be around 1 × 10 28 molec. s -1 between May and July. Observations conducted with the IRAM 30-m radio telescope in May and July 2005 resulted in detections of HCN, CH 3 OH and H 2 S with classical abundances relative to water (0.12, 2.7 and 0.5%, respectively). In addition, a variation of the HCN production rate with a period of 1.73 ± 0.10 days was observed in May 2005, consistent with the 1.7-day rotation period of the nucleus. The phase of these variations, as well as those of CN seen in July by Jehin et al. [Jehin, E., Manfroid, J., Hutsemékers, D., Cochran, A.L., Arpigny, C., Jackson, W.M., Rauer, H., Schulz, R., Zucconi, J.-M., 2006. Astrophys. J. 641, L145-L148], is consistent with a rotation period of the nucleus of 1.715 days and a strong variation of the outgassing activity by a factor 3 from minimum to maximum. This also implies that the impact took place on the rising phase of the "natural" outgassing which reached its maximum ≈4 h after the impact. Post-impact observations at IRAM and CSO did not reveal a significant change of the outgassing rates and relative abundances, with the exception of CH 3 OH which may have been more abundant by up to one order of magnitude in the ejecta. Most other variations are linked to the intrinsic variability of the comet. The Odin satellite monitored nearly continuously the H 2 O line at 557 GHz during the 38 h following the impact on the 4th of July, in addition to weekly monitoring. Once the periodic variations related to the nucleus rotation are removed, a small increase of outgassing related to the impact is present, which corresponds to the release of ≈ 5000 ± 2000 tons of water. Two other bursts of activity, also observed at other wavelengths, were seen on 23 June and 7 July; they correspond to even larger releases of gas. © 2006 Elsevier Inc. All rights reserved.
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| 27. |
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| 28. |
- Coombes, Brandon J, et al.
(author)
-
Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study.
- 2021
-
In: Complex psychiatry. - : S. Karger AG. - 2673-3005 .- 2673-298X. ; 7:3-4, s. 80-89
-
Journal article (peer-reviewed)abstract
- Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = -0.14; 95% confidence interval [CI]: -0.24 to -0.03; p value = 0.010) and MDD (β = -0.16; 95% CI: -0.27 to -0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34-1.93; p value = 2e-7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.
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| 29. |
- Crovisier, J., et al.
(author)
-
The chemical composition of 9P/tempel 1 from radio observations
- 2009
-
In: ESO Astrophysics Symposia. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 1431-2433 .- 1611-6143. - 9783540769583 ; 2009, s. 243-248
-
Conference paper (peer-reviewed)abstract
- In 2005, as part of a world-wide multi-wavelength investigation of comet 9P/Tempel 1 in support to the Deep Impact mission, we conducted radio spectroscopic observations with the Nançay radio telescope, the Odin satellite, the CSO 10-m and the IRAM 30-m telescopes. We report here our results concerning the chemical composition of the comet. The relative abundances of the detected species (H2O, CH3OH, H2S, HCN) or their upper limits (CO, H2CO, CS) are comparable to the mean values observed in other comets. No significant changes of the outgassing rates (except possibly for CH3OH) or of the molecular abundances were observed following the impact.
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| 30. |
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| 31. |
- Herrera-Rivero, Marisol, et al.
(author)
-
Exploring the genetics of lithium response in bipolar disorders.
- 2023
-
In: Research square.
-
Other publication (other academic/artistic)abstract
- Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
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| 32. |
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| 33. |
- Hou, Liping, et al.
(author)
-
Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
-
In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
-
Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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| 34. |
- Kalman, Janos L, et al.
(author)
-
Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
-
In: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
-
Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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| 35. |
- Kraemer, Benjamin M., et al.
(author)
-
Climate change drives widespread shifts in lake thermal habitat
- 2021
-
In: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 11:6, s. 521-529
-
Journal article (peer-reviewed)abstract
- Lake surfaces are warming worldwide, raising concerns about lake organism responses to thermal habitat changes. Species may cope with temperature increases by shifting their seasonality or their depth to track suitable thermal habitats, but these responses may be constrained by ecological interactions, life histories or limiting resources. Here we use 32 million temperature measurements from 139 lakes to quantify thermal habitat change (percentage of non-overlap) and assess how this change is exacerbated by potential habitat constraints. Long-term temperature change resulted in an average 6.2% non-overlap between thermal habitats in baseline (1978-1995) and recent (1996-2013) time periods, with non-overlap increasing to 19.4% on average when habitats were restricted by season and depth. Tropical lakes exhibited substantially higher thermal non-overlap compared with lakes at other latitudes. Lakes with high thermal habitat change coincided with those having numerous endemic species, suggesting that conservation actions should consider thermal habitat change to preserve lake biodiversity. Using measurements from 139 global lakes, the authors demonstrate how long-term thermal habitat change in lakes is exacerbated by species' seasonal and depth-related constraints. They further reveal higher change in tropical lakes, and those with high biodiversity and endemism.
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| 36. |
- Ou, Anna H., et al.
(author)
-
Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study
- 2024
-
In: TRANSLATIONAL PSYCHIATRY. - 2158-3188. ; 14:1
-
Journal article (peer-reviewed)abstract
- Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
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| 37. |
- Refolo, P., et al.
(author)
-
On the normativity of evidence - Lessons from philosophy of science and the "VALIDATE" project
- 2023
-
In: European Review for Medical and Pharmacological Sciences. - : VERDUCI PUBLISHER. - 1128-3602. ; 27:23, s. 11202-11210
-
Journal article (peer-reviewed)abstract
- "Evidence" is a key term in medicine and health services research, including Health Technology Assessment (HTA). Randomized clinical trials (RCTs) have undoubtedly dominated the scene of generating evidence for a long period of time, becoming the hallmark of evidence-based medicine (EBM). However, due to a number of misunderstandings, the lay audience and some researchers have sometimes placed too much trust in RCTs compared to other methods of investigation. One of the principal misunderstandings is to consider RCTs findings as isolated and self -apparent pieces of information. In other words, what has been essentially lacking was the awareness of the value-context of the evidence and, in particular, the value-and theory-ladenness (normativity) of scientific knowledge. This paper aims to emphasize the normativity that exists in the production of scientific knowledge, and in particular in the conduct of RCTs as well as in the performance of HTA. The work is based on some lessons learned from Philosophy of Science and the European project "VALIDATE" (VALues In Doing Assessments of healthcare TEchnologies"). VALIDATE was a three-year EU Erasmus+ strategic partnerships project (20182021), in which training in the field of HTA was further optimized by using insights from political science and ethics (in accordance with the recent definition of HTA). Our analysis may reveal useful insights for addressing some challenges that HTA is going to face in the future.
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| 38. |
- Urrutia-Cordero, P., et al.
(author)
-
SITES AquaNet: An open infrastructure for mesocosm experiments with high frequency sensor monitoring across lakes
- 2021
-
In: Limnology and Oceanography-Methods. - : Wiley. - 1541-5856. ; 19:6, s. 385-400
-
Journal article (peer-reviewed)abstract
- For aquatic scientists mesocosm experiments are important tools for hypothesis testing as they offer a compromise between experimental control and realism. Here we present a new mesocosm infrastructure-SITES AquaNET-located in five lakes connected to field stations in Sweden that cover a similar to 760 km latitudinal gradient. SITES AquaNet overcomes major hindrances in aquatic experimental research through: (i) openness to the scientific community, (ii) the potential to implement coordinated experiments across sites and time, and (iii) high-frequency measurements (temperature, photosynthetic photon flux density, turbidity and dissolved oxygen, chlorophyll a and phycocyanin concentrations) with an autonomous sensor system. Moreover, the infrastructure provides operational guidance and sensor expertise from technical staff, and connections to a multi-layered monitoring programme ("SITES Water") for each lake. This enables ecological observations from whole lake ecosystems to be compared with experimental studies aiming at disentangling major drivers and mechanisms underlying observed changes. Here we describe the technical properties of the infrastructure along with possibilities for experimental manipulations to tackle pressing issues in aquatic ecology and global change science. As a proof of concept, we also present a first mesocosm experiment across all five field sites with a cross-factorial design to evaluate responses of the sensor measurements to press/bottom-up (constant light reduction) and pulse/top-down (temporary fish predation) disturbances. This demonstrates the suitability of the infrastructure and autonomous sensor system to host modularized experiments and exemplifies the power and advantages of the approach to integrate a network of mecsocosm facilities with manageable costs across large geographic areas.
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