| 1. |
- Coombes, Brandon J, et al.
(författare)
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Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study.
- 2021
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Ingår i: Complex psychiatry. - : S. Karger AG. - 2673-3005 .- 2673-298X. ; 7:3-4, s. 80-89
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Hartkopf, Andreas D., et al.
(författare)
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Disseminated tumour cells from the bone marrow of early breast cancer patients : Results from an international pooled analysis
- 2021
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 154, s. 128-137
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC. Experimental design: Individual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival of DTC-positive versus DTC-negative patients. Results: In total, 10,307 patients were included. Of these, 2814 (27.3%) were DTC-positive. DTC detection was associated with higher tumour grade, larger tumour size, nodal positivity, oestrogen receptor and progesterone receptor negativity, and HER2 positivity (all p < 0.001). Multivariate analyses showed that DTC detection was an independent prognostic marker for overall survival, disease-free survival and distant disease-free survival with hazard ratios (HR) and 95% confidence intervals (CI) of 1.23 (95% CI: 1.06–1.43, p = 0.006), 1.30 (95% CI: 1.12–1.52, p < 0.001) and 1.30 (95% CI: 1.08–1.56, p = 0.006), respectively. There was no association between locoregional relapse-free survival and DTC detection (HR 1.21; 95% CI 0.68–2.16; p = 0.512). Conclusions: DTCs in the BM represent an independent prognostic marker in patients with EBC. The heterogeneous metastasis-initiating potential of DTCs is consistent with the concept of cancer dormancy.
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| 3. |
- Jolly, Jean Baptiste, 1990, et al.
(författare)
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ALMA Lensing Cluster Survey: A spectral stacking analysis of [C II] in lensed z similar to 6 galaxies
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 652
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Tidskriftsartikel (refereegranskat)abstract
- Context. The properties of galaxies at redshift z>6 hold the key to our understanding of the early stages of galaxy evolution and can potentially identify the sources of the ultraviolet radiation that give rise to the epoch of reionisation. The far-infrared cooling line of [C II] at 158 mu m is known to be bright and correlate with the star formation rate (SFR) of low-redshift galaxies, and hence is also suggested to be an important tracer of star formation and interstellar medium properties for very high-redshift galaxies. Aims. With the aim to study the interstellar medium properties of gravitationally lensed galaxies at z>6, we search for [C II] and thermal dust emission in a sample of 52 > 6 galaxies observed by the ALMA Lensing Cluster Survey. Methods. We perform our analysis using LINESTACKER, stacking both [C II] and continuum emission. The target sample is selected from multiple catalogues, and the sample galaxies have spectroscopic redshift or low-uncertainty photometric redshifts (sigma(z)<0.02) in nine galaxy clusters. Source properties of the target galaxies are either extracted from the literature or computed using spectral energy distribution fitting. Both weighted-average and median stacking are used, on both the full sample and three sub-samples. Results. Our analyses find no detection of either [C II] or continuum. An upper limit on L-[CII] is derived, implying that [C II] remains marginally consistent for low-SFR z>6 galaxies but likely is under-luminous compared to the local L-[CII]-SFR relationship. We discuss potential biases and possible physical effects that may be the cause of the non-detection. Further, the upper limit on the dust continuum implies that less than half of the star formation is obscured.
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| 4. |
- Lamarre, Jean François, et al.
(författare)
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Timing of Breeding Site Availability Across the North-American Arctic Partly Determines Spring Migration Schedule in a Long-Distance Neotropical Migrant
- 2021
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Ingår i: Frontiers in Ecology and Evolution. - : Frontiers Media SA. - 2296-701X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Long-distance migrants are under strong selection to arrive on their breeding grounds at a time that maximizes fitness. Many arctic birds start nesting shortly after snow recedes from their breeding sites and timing of snowmelt can vary substantially over the breeding range of widespread species. We tested the hypothesis that migration schedules of individuals co-occurring at the same non-breeding areas are adapted to average local environmental conditions encountered at their specific and distant Arctic breeding locations. We predicted that timing of breeding site availability (measured here as the average snow-free date) should explain individual variation in departure time from shared non-breeding areas. We tested our prediction by tracking American Golden-Plovers (Pluvialis dominica) nesting across the North-American Arctic. These plovers use a non-breeding (wintering) area in South America and share a spring stopover area in the nearctic temperate grasslands, located >1,800 km away from their nesting locations. As plovers co-occur at the same non-breeding areas but use breeding sites segregated by latitude and longitude, we could disentangle the potential confounding effects of migration distance and timing of breeding site availability on individual migration schedule. As predicted, departure date of individuals stopping-over in sympatry was positively related to the average snow-free date at their respective breeding location, which was also related to individual onset of incubation. Departure date from the shared stopover area was not explained by the distance between the stopover and the breeding location, nor by the stopover duration of individuals. This strongly suggests that plover migration schedule is adapted to and driven by the timing of breeding site availability per se. The proximate mechanism underlying the variable migration schedule of individuals is unknown and may result from genetic differences or individual learning. Temperatures are currently changing at different speeds across the Arctic and this likely generates substantial heterogeneity in the strength of selection pressure on migratory schedule of arctic birds migrating sympatrically.
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| 5. |
- Martin-Loeches, Ignacio, et al.
(författare)
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The importance of airway and lung microbiome in the critically ill
- 2020
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Ingår i: Critical Care. - : BMC. - 1364-8535 .- 1466-609X. ; 24:1
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Forskningsöversikt (refereegranskat)abstract
- During critical illness, there are a multitude of forces such as antibiotic use, mechanical ventilation, diet changes and inflammatory responses that could bring the microbiome out of balance. This so-called dysbiosis of the microbiome seems to be involved in immunological responses and may influence outcomes even in individuals who are not as vulnerable as a critically ill ICU population. It is therefore probable that dysbiosis of the microbiome is a consequence of critical illness and may, subsequently, shape an inadequate response to these circumstances. Bronchoscopic studies have revealed that the carina represents the densest site of bacterial DNA along healthy airways, with a tapering density with further bifurcations. This likely reflects the influence of micro-aspiration as the primary route of microbial immigration in healthy adults. Though bacterial DNA density grows extremely sparse at smaller airways, bacterial signal is still consistently detectable in bronchoalveolar lavage fluid, likely reflecting the fact that lavage via a wedged bronchoscope samples an enormous surface area of small airways and alveoli. The dogma of lung sterility also violated numerous observations that long predated culture-independent microbiology. The bodys resident microbial consortia (gut and/or respiratory microbiota) affect normal host inflammatory and immune response mechanisms. Disruptions in these host-pathogen interactions have been associated with infection and altered innate immunity. In this narrative review, we will focus on the rationale and current evidence for a pathogenic role of the lung microbiome in the exacerbation of complications of critical illness, such as acute respiratory distress syndrome and ventilator-associated pneumonia.
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| 6. |
- Osuchowski, Marcin F., et al.
(författare)
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The COVID-19 puzzle : deciphering pathophysiology and phenotypes of a new disease entity
- 2021
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Ingår i: The Lancet Respiratory Medicine. - : Elsevier. - 2213-2600 .- 2213-2619. ; 9:6, s. 622-642
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Forskningsöversikt (refereegranskat)abstract
- The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into the epidemiology of COVID-19, important questions remain about the clinical complexities and underlying mechanisms of disease phenotypes. Severe COVID-19 most commonly involves respiratory manifestations, although other systems are also affected, and acute disease is often followed by protracted complications. Such complex manifestations suggest that SARS-CoV-2 dysregulates the host response, triggering wide-ranging immuno-inflammatory, thrombotic, and parenchymal derangements. We review the intricacies of COVID-19 pathophysiology, its various phenotypes, and the anti-SARS-CoV-2 host response at the humoral and cellular levels. Some similarities exist between COVID-19 and respiratory failure of other origins, but evidence for many distinctive mechanistic features indicates that COVID-19 constitutes a new disease entity, with emerging data suggesting involvement of an endotheliopathy-centred pathophysiology. Further research, combining basic and clinical studies, is needed to advance understanding of pathophysiological mechanisms and to characterise immuno-inflammatory derangements across the range of phenotypes to enable optimum care for patients with COVID-19.
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| 7. |
- Schweinsberg, Martin, et al.
(författare)
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Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
- 2021
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Ingår i: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
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Tidskriftsartikel (refereegranskat)abstract
- In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
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| 8. |
- Sun, Fengwu, et al.
(författare)
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Extensive Lensing Survey of Optical and Near-infrared Dark Objects (El Sonido): HST H-faint Galaxies behind 101 Lensing Clusters
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 922:2
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Tidskriftsartikel (refereegranskat)abstract
- We present a Spitzer/IRAC survey of H-faint (H-160 greater than or similar to 26.4, < 5 sigma) sources in 101 lensing cluster fields. Across a CANDELS/Wide-like survey area of similar to 648 arcmin(2) (effectively similar to 221 arcmin(2) in the source plane), we have securely discovered 53 sources in the IRAC Channel-2 band (CH2, 4.5 mu m; median CH2 = 22.46 +/- 0.11 AB mag) that lack robust HST/WFC3-IR F160W counterparts. The most remarkable source in our sample, namely ES-009 in the field of Abell 2813, is the brightest H-faint galaxy at 4.5 mu m known so far (CH2 = 20.48 +/- 0.03 AB mag). We show that the H-faint sources in our sample are massive (median M-star = 10 10.3 +/- 0.3 M-circle dot, star-forming (median star formation rate =1001 M-circle dot yr(-1)), and dust-obscured (A(v) = 2.6 +/- 0.3) galaxies around a median photometric redshift of z = 3.9 +/- 0.4. The stellar continua of 14 H-faint galaxies can be resolved in the CH2 band, suggesting a median circularized effective radius (R-e,R-circ; lensing corrected) of 1.9 +/- 0.2 kpc and <1.5 kpc for the resolved and whole samples, respectively. This is consistent with the sizes of massive unobscured galaxies at z similar to 4, indicating that H-faint galaxies represent the dusty tail of the distribution of a wider galaxy population. Comparing with the ALMA dust continuum sizes of similar galaxies reported previously, we conclude that the heavy dust obscuration in H-faint galaxies is related to the compactness of both stellar and dust continua (R-e,R-circ similar to 1 kpc). These H-faint galaxies make up 161 3 % of the galaxies in the stellar-mass range of 10(10) - 10(11.2) M-circle dot at z = 3 similar to 5, contributing to 8(-4)(+8)% of the cosmic star formation rate density in this epoch and likely tracing the early phase of massive galaxy formation.
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