| 1. |
- Hawthorn, F., et al.
(author)
-
TOI-836: A super-Earth and mini-Neptune transiting a nearby K-dwarf
- 2023
-
In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 520:3, s. 3649-3668
-
Journal article (peer-reviewed)abstract
- We present the discovery of two exoplanets transiting TOI-836 (TIC 440887364) using data from TESS Sector 11 and Sector 38. TOI-836 is a bright (T = 8.5 mag), high proper motion (∼200 mas yr−1), low metallicity ([Fe/H]≈−0.28) K-dwarf with a mass of 0.68 ± 0.05 M and a radius of 0.67 ± 0.01 R. We obtain photometric follow-up observations with a variety of facilities, and we use these data sets to determine that the inner planet, TOI-836 b, is a 1.70 ± 0.07 R super-Earth in a 3.82-d orbit, placing it directly within the so-called ‘radius valley’. The outer planet, TOI-836 c, is a 2.59 ± 0.09 R mini-Neptune in an 8.60-d orbit. Radial velocity measurements reveal that TOI-836 b has a mass of 4.5 ± 0.9 M, while TOI-836 c has a mass of 9.6 ± 2.6 M. Photometric observations show Transit Timing Variations (TTVs) on the order of 20 min for TOI-836 c, although there are no detectable TTVs for TOI-836 b. The TTVs of planet TOI-836 c may be caused by an undetected exterior planet.
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| 2. |
- Duffy, J. M. N., et al.
(author)
-
Top 10 priorities for future infertility research: an international consensus development study
- 2020
-
In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 35:12, s. 2715-2724
-
Journal article (peer-reviewed)abstract
- STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties was entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI and IVF) and ethics, access and organization of care were identified during a consensus development meeting involving 41 participants from I I countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research and population science. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgment and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, will help research funding organizations and researchers to develop their future research agenda.
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| 3. |
- Crenshaw, D. M., et al.
(author)
-
Multiwavelength observations of short-timescale variability in NGC 4151. I. Ultraviolet observations
- 1996
-
In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 470:1, s. 322-335335
-
Journal article (peer-reviewed)abstract
- Presents the results of an intensive ultraviolet monitoring campaign on the Seyfert 1 galaxy NGC 4151, as part of an effort to study its short-timescale variability over a broad range in wavelength. The nucleus of NGC 4151 was observed continuously with the International Ultraviolet Explorer for 9.3 days, yielding a pair of LWP and SWP spectra every ~70 minutes, and during 4 hr periods for 4 days prior to and 5 days after the continuous-monitoring period. The sampling frequency of the observations is an order of magnitude higher than that of any previous UV monitoring campaign on a Seyfert galaxy. The continuum fluxes in bands from 1275 to 2688 Aring went through four significant and well-defined ldquoeventsrdquo of duration 2-3 days during the continuous-monitoring period. The authors find that the amplitudes of the continuum variations decrease with increasing wavelength, which extends a general trend for this and other Seyfert galaxies to smaller timescales (i.e., a few days). The continuum variations in all the UV bands are simultaneous to within an accuracy of ~0.15 days, providing a strict constraint on continuum models. The emission-line light curves show only one major event during the continuous monitoring (a slow rise followed by a shallow dip) and do not correlate well with continuum light curves over the short duration of the campaign, because the timescale for continuum variations is apparently smaller than the response times of the emission lines
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| 4. |
- De Rosa, G., et al.
(author)
-
Velocity-resolved Reverberation Mapping of Five Bright Seyfert 1 Galaxies
- 2018
-
In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 866:2
-
Journal article (peer-reviewed)abstract
- We present the first results from a reverberation-mapping campaign undertaken during the first half of 2012, with additional data on one active galactic nucleus (AGN) (NGC 3227) from a 2014 campaign. Our main goals are (1) to determine the black hole masses from continuum-H beta reverberation signatures, and (2) to look for velocity-dependent time delays that might be indicators of the gross kinematics of the broad-line region. We successfully measure H beta time delays and black hole masses for five AGNs, four of which have previous reverberation mass measurements. The values measured here are in agreement with earlier estimates, though there is some intrinsic scatter beyond the formal measurement errors. We observe velocity-dependent H beta lags in each case, and find that the patterns have changed in the intervening five years for three AGNs that were also observed in 2007.
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| 5. |
- Edelson, R. A., et al.
(author)
-
Multiwavelength observations of short-timescale variability in NGC 4151. IV. Analysis of multiwavelength continuum variability
- 1996
-
In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 470:1, s. 364-377377
-
Journal article (peer-reviewed)abstract
- For pt.III see ibid., vol.470, no.1, p.349-63 (1996). Combines data from the three preceding papers in order to analyze the multi wave-band variability and spectral energy distribution of the Seyfert 1 galaxy NGC 4151 during the 1993 December monitoring campaign. The source, which was near its peak historical brightness, showed strong, correlated variability at X-ray, ultraviolet, and optical wavelengths. The strongest variations were seen in medium-energy (~1.5 keV) X-rays, with a normalized variability amplitude (NVA) of 24%. Weaker (NVA=6%) variations (uncorrelated with those at lower energies) were seen at soft gamma-ray energies of ~100 keV. No significant variability was seen in softer (0.1-1 keV) X-ray bands. In the ultraviolet/optical regime, the NVA decreased from 9% to 1% as the wavelength increased from 1275 to 6900 Aring. These data do not probe extreme ultraviolet (1200 Aring to 0.1 keV) or hard X-ray (250 keV) variability. The phase differences between variations in different bands were consistent with zero lag, with upper limits of lsim0.15 day between 1275 Aring and the other ultraviolet bands, lsim0.3 day between 1275 Aring and 1.5 keV, and lsim1 day between 1275 and 5125 Aring. These tight limits represent more than an order of magnitude improvement over those determined in previous multi-wave-band AGN monitoring campaigns. The ultraviolet fluctuation power spectra showed no evidence for periodicity, but were instead well fitted with a very steep, red power law (ales-2.5)
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| 6. |
- Gould, A., et al.
(author)
-
MOA-2010-BLG-523:" Failed Planet"= RS CVn Star
- 2013
-
In: Astrophysical Journal. - 0004-637X. ; 763:2
-
Journal article (peer-reviewed)abstract
- The Galactic bulge source MOA-2010-BLG-523S exhibited short-term deviations from a standard microlensing light curve near the peak of an A(max) similar to 265 high-magnification microlensing event. The deviations originally seemed consistent with expectations for a planetary companion to the principal lens. We combine long-term photometric monitoring with a previously published high-resolution spectrum taken near peak to demonstrate that this is an RS CVn variable, so that planetary microlensing is not required to explain the light-curve deviations. This is the first spectroscopically confirmed RS CVn star discovered in the Galactic bulge.
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| 7. |
- Kalter, J., et al.
(author)
-
Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer : An individual patient data meta-analysis of 22 RCTs
- 2018
-
In: Psycho-Oncology. - : WILEY. - 1057-9249 .- 1099-1611. ; 27:4, s. 1150-1161
-
Research review (peer-reviewed)abstract
- Objective: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. Methods: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables.Results: PSI significantly improved QoL (=0.14,95%CI=0.06;0.21), EF ( beta = 0.13,95%CI = 0.05;0.20), and SF (beta = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. Conclusions: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.
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| 8. |
- Lam, MT, et al.
(author)
-
A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function
- 2019
-
In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 216:12, s. 2778-2799
-
Journal article (peer-reviewed)abstract
- Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated immune cells and is associated with a variable clinical spectrum having overlap with more common pathophysiologies. HLH is difficult to diagnose and can be part of inflammatory syndromes. Here, we identify a novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. Patients shared the same de novo CDC42 mutation (Chr1:22417990C>T, p.R186C) and altered hematopoietic compartment, immune dysregulation, and inflammation. CDC42 mutations had been associated with syndromic neurodevelopmental disorders. In vitro and in vivo assays documented unique effects of p.R186C on CDC42 localization and function, correlating with the distinctiveness of the trait. Emapalumab was critical to the survival of one patient, who underwent successful bone marrow transplantation. Early recognition of the disorder and establishment of treatment followed by bone marrow transplant are important to survival.
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| 9. |
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| 10. |
- Korth, J., et al.
(author)
-
TOI-1130: A photodynamical analysis of a hot Jupiter in resonance with an inner low-mass planet
- 2023
-
In: Astronomy & Astrophysics. - 1432-0746 .- 0004-6361. ; 675
-
Journal article (peer-reviewed)abstract
- The TOI-1130 is a known planetary system around a K-dwarf consisting of a gas giant planet, TOI-1130 c on an 8.4-day orbit that is accompanied by an inner Neptune-sized planet, TOI-1130 b, with an orbital period of 4.1 days. We collected precise radial velocity (RV) measurements of TOI-1130 with the HARPS and PFS spectrographs as part of our ongoing RV follow-up program. We performed a photodynamical modeling of the HARPS and PFS RVs, along with transit photometry from the Transiting Exoplanet Survey Satellite (TESS) and the TESS Follow-up Observing Program (TFOP). We determined the planet masses and radii of TOI-1130 b and TOI-1130 c to be Mb = 19.28 ± 0.97M⊕ and Rb = 3.56 ± 0.13 R⊕, and Mc = 325.59 ± 5.59M⊕ and Rc = 13.32−1.41+1.55 R⊕, respectively. We have spectroscopically confirmed the existence of TOI-1130 b, which had previously only been validated. We find that the two planets have orbits with small eccentricities in a 2:1 resonant configuration. This is the first known system with a hot Jupiter and an inner lower mass planet locked in a mean-motion resonance. TOI-1130 belongs to the small, yet growing population of hot Jupiters with an inner low-mass planet that poses a challenge to the pathway scenario for hot Jupiter formation. We also detected a linear RV trend that is possibly due to the presence of an outer massive companion.
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| 11. |
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| 12. |
- Patel, Riyaz S., et al.
(author)
-
Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
-
In: Circulation. - 2574-8300. ; 12:4
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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| 13. |
- Schunkert, Heribert, et al.
(author)
-
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
- 2011
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:4, s. 153-333
-
Journal article (peer-reviewed)abstract
- We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
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| 14. |
- Bouwmeester, S, et al.
(author)
-
Registered Replication Report: Rand, Greene, and Nowak (2012) : Multilab direct replication of: Study 7 from Rand, D. G., Greene, J. D., & Nowak, M. A. (2012) Spontaneous giving and calculated greed. Nature, 489, 427–430.
- 2017
-
In: Perspectives on Psychological Science. - : Sage Publications. - 1745-6916 .- 1745-6924. ; 12:3, s. 527-542
-
Journal article (peer-reviewed)abstract
- In an anonymous 4-person economic game, participants contributed more money to a common project (i.e., cooperated) when required to decide quickly than when forced to delay their decision (Rand, Greene & Nowak, 2012), a pattern consistent with the social heuristics hypothesis proposed by Rand and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned to conditions and who met the protocol inclusion criteria (an intent-to-treat approach that included the 65.9% of participants in the time-pressure condition and 7.5% in the forced-delay condition who did not adhere to the time constraints), and we observed a difference in contributions of −0.37 percentage points compared with an 8.6 percentage point difference calculated from the original data. Analyzing the data as the original article did, including data only for participants who complied with the time constraints, the RRR observed a 10.37 percentage point difference in contributions compared with a 15.31 percentage point difference in the original study. In combination, the results of the intent-to-treat analysis and the compliant-only analysis are consistent with the presence of selection biases and the absence of a causal effect of time pressure on cooperation.
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| 15. |
- Bouwmeester, Sjoerd, et al.
(author)
-
Registered Replication Report : Rand, Greene, and Nowak (2012)
- 2017
-
In: Perspectives on Psychological Science. - : SAGE Publications. - 1745-6916 .- 1745-6924. ; 12:3, s. 527-542
-
Journal article (peer-reviewed)abstract
- In an anonymous 4-person economic game, participants contributed more money to a common project (i.e., cooperated) when required to decide quickly than when forced to delay their decision (Rand, Greene & Nowak, 2012), a pattern consistent with the social heuristics hypothesis proposed by Rand and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned to conditions and who met the protocol inclusion criteria (an intent-to-treat approach that included the 65.9% of participants in the time-pressure condition and 7.5% in the forced-delay condition who did not adhere to the time constraints), and we observed a difference in contributions of −0.37 percentage points compared with an 8.6 percentage point difference calculated from the original data. Analyzing the data as the original article did, including data only for participants who complied with the time constraints, the RRR observed a 10.37 percentage point difference in contributions compared with a 15.31 percentage point difference in the original study. In combination, the results of the intent-to-treat analysis and the compliant-only analysis are consistent with the presence of selection biases and the absence of a causal effect of time pressure on cooperation.
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| 16. |
- Buffart, L. M., et al.
(author)
-
Effects and moderators of coping skills training on symptoms of depression and anxiety in patients with cancer : Aggregate data and individual patient data meta-analyses
- 2020
-
In: Clinical Psychology Review. - : Elsevier BV. - 0272-7358 .- 1873-7811. ; 80
-
Research review (peer-reviewed)abstract
- PURPOSE: This study evaluated the effects of coping skills training (CST) on symptoms of depression and anxiety in cancer patients, and investigated moderators of the effects.METHODS: Overall effects and intervention-related moderators were studied in meta-analyses of pooled aggregate data from 38 randomized controlled trials (RCTs). Patient-related moderators were examined using linear mixed-effect models with interaction tests on pooled individual patient data (n = 1953) from 15 of the RCTs.RESULTS: CST had a statistically significant but small effect on depression (g = -0.31,95% confidence interval (CI) = -0.40;-0.22) and anxiety (g = -0.32,95%CI = -0.41;-0.24) symptoms. Effects on depression symptoms were significantly larger for interventions delivered face-to-face (p = .003), led by a psychologist (p = .02) and targeted to patients with psychological distress (p = .002). Significantly larger reductions in anxiety symptoms were found in younger patients (pinteraction < 0.025), with the largest reductions in patients <50 years (β = -0.31,95%CI = -0.44;-0.18) and no significant effects in patients ≥70 years. Effects of CST on depression (β = -0.16,95%CI = -0.25;-0.07) and anxiety (β = -0.24,95%CI = -0.33;-0.14) symptoms were significant in patients who received chemotherapy but not in patients who did not (pinteraction < 0.05).CONCLUSIONS: CST significantly reduced symptoms of depression and anxiety in cancer patients, and particularly when delivered face-to-face, provided by a psychologist, targeted to patients with psychological distress, and given to patients who were younger and received chemotherapy.
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| 17. |
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| 18. |
- Holmes, Michael V., et al.
(author)
-
Secretory Phospholipase A(2)-IIA and Cardiovascular Disease
- 2013
-
In: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:21, s. 1966-1976
-
Journal article (peer-reviewed)abstract
- Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. less thanbrgreater than less thanbrgreater thanBackground Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. less thanbrgreater than less thanbrgreater thanMethods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA(2)-IIA isoenzyme, as an instrumental variable. less thanbrgreater than less thanbrgreater thanResults PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA(2)-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. less thanbrgreater than less thanbrgreater thanConclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.
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| 19. |
- Horne, B D, et al.
(author)
-
Pharmacogenetic warfarin dose refinements remain significantly influenced by genetic factors after one week of therapy
- 2012
-
In: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 107:2, s. 232-240
-
Journal article (peer-reviewed)abstract
- By guiding initial warfarin dose, pharmacogenetic (PGx) algorithms may improve the safety of warfarin initiation. However, once international normalised ratio (INR) response is known, the contribution of PGx to dose refinements is uncertain. This study sought to develop and validate clinical and PGx dosing algorithms for warfarin dose refinement on days 6-11 after therapy initiation. An international sample of 2,022 patients at 13 medical centres on three continents provided clinical, INR, and genetic data at treatment days 6-11 to predict therapeutic warfarin dose. Independent derivation and retrospective validation samples were composed by randomly dividing the population (80%/20%). Prior warfarin doses were weighted by their expected effect on S-warfarin concentrations using an exponential-decay pharmacokinetic model. The INR divided by that "effective" dose constituted a treatment response index . Treatment response index, age, amiodarone, body surface area, warfarin indication, and target INR were associated with dose in the derivation sample. A clinical algorithm based on these factors was remarkably accurate: in the retrospective validation cohort its R2 was 61.2% and median absolute error (MAE) was 5.0 mg/week. Accuracy and safety was confirmed in a prospective cohort (N=43). CYP2C9 variants and VKORC1-1639 G→A were significant dose predictors in both the derivation and validation samples. In the retrospective validation cohort, the PGx algorithm had: R2= 69.1% (p<0.05 vs. clinical algorithm), MAE= 4.7 mg/week. In conclusion, a pharmacogenetic warfarin dose-refinement algorithm based on clinical, INR, and genetic factors can explain at least 69.1% of therapeutic warfarin dose variability after about one week of therapy.
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| 20. |
- Lenzini, P., et al.
(author)
-
Integration of genetic, clinical, and INR data to refine warfarin dosing
- 2010
-
In: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 87:5, s. 572-578
-
Journal article (peer-reviewed)abstract
- Well-characterized genes that affect warfarin metabolism (cytochrome P450 (CYP) 2C9) and sensitivity (vitamin K epoxide reductase complex 1 (VKORC1)) explain one-third of the variability in therapeutic dose before the international normalized ratio (INR) is measured. To determine genotypic relevance after INR becomes available, we derived clinical and pharmacogenetic refinement algorithms on the basis of INR values (on day 4 or 5 of therapy), clinical factors, and genotype. After adjusting for INR, CYP2C9 and VKORC1 genotypes remained significant predictors (P < 0.001) of warfarin dose. The clinical algorithm had an R(2) of 48% (median absolute error (MAE): 7.0 mg/week) and the pharmacogenetic algorithm had an R(2) of 63% (MAE: 5.5 mg/week) in the derivation set (N = 969). In independent validation sets, the R(2) was 26-43% with the clinical algorithm and 42-58% when genotype was added (P = 0.002). After several days of therapy, a pharmacogenetic algorithm estimates the therapeutic warfarin dose more accurately than one using clinical factors and INR response alone.
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| 21. |
- Pappas, D. A., et al.
(author)
-
Prevalence of cardiovascular disease and major risk factors in patients with rheumatoid arthritis: a multinational cross-sectional study
- 2018
-
In: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 37:9, s. 2331-2340
-
Journal article (peer-reviewed)abstract
- To compare the prevalence of cardiovascular disease (CVD) and major CVD risk factors among rheumatoid arthritis (RA) patients enrolled in a large US and multinational registry. We compared CVD and CVD risk factor prevalence from 11 countries enrolled in the CORRONA US and CORRONA International registries; patients from the 10 ex-US participating countries were grouped by region (Eastern Europe, Latin America, and India). Unadjusted summary data were presented for demographics and disease characteristics; comparisons for prevalence of CVD risk factors and CVD were age/gender standardized to the age/gender distribution of the US enrolled patients. Overall, 25,987 patients were included in this analysis. Compared to patients from the ex-US regions, US participants had longer disease duration and lower disease activity, yet were more likely to receive a biologic agent. Additionally, CORRONA US participants had the highest body mass index (BMI). Enrolled patients in India had the lowest BMI, were more rarely smokers, and had a low prevalence of hyperlipidemia, hypertension, and prior CVD compared to the US and other ex-US regions. Participants from Eastern Europe had a higher prevalence of hypertension and hyperlipidemia and highest prevalence of all manifestations of CVD. Differences in the prevalence of both CVD and major CVD risk factors were observed across the four regions investigated. Observed differences may be influenced by variations in both non-modifiable/modifiable characteristics of patient populations, and may contribute to heterogeneity on the observed safety of investigational and approved therapies in studies involving RA patients from different origins.
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| 22. |
- Parviainen, H., et al.
(author)
-
TOI-2266 b: A keystone super-Earth at the edge of the M dwarf radius valley
- 2024
-
In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 683
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Journal article (peer-reviewed)abstract
- We validate the Transiting Exoplanet Survey Satellite (TESS) object of interest TOI-2266.01 (TIC 8348911) as a small transiting planet (most likely a super-Earth) orbiting a faint M5 dwarf (V = 16.54) on a 2.33 d orbit. The validation is based on an approach where multicolour transit light curves are used to robustly estimate the upper limit of the transiting object's radius. Our analysis uses SPOC-pipeline TESS light curves from Sectors 24, 25, 51, and 52, simultaneous multicolour transit photometry observed with MuSCAT2, MuSCAT3' and HiPERCAM, and additional transit photometry observed with the LCOGT telescopes. TOI-2266 b is found to be a planet with a radius of 1.54 ± 0.09 R, which locates it at the edge of the transition zone between rocky planets, water-rich planets, and sub-Neptunes (the so-called M dwarf radius valley). The planet is amenable to ground-based radial velocity mass measurement with red-sensitive spectrographs installed in large telescopes, such as MAROON-X and Keck Planet Finder (KPF), which makes it a valuable addition to a relatively small population of planets that can be used to probe the physics of the transition zone. Further, the planet's orbital period of 2.33 days places it inside a 'keystone planet'wedge in the period-radius plane where competing planet formation scenarios make conflicting predictions on how the radius valley depends on the orbital period. This makes the planet also a welcome addition to the small population of planets that can be used to test small-planet formation scenarios around M dwarfs.
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| 23. |
- Patel, Riyaz S., et al.
(author)
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Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
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In: Circulation. - 2574-8300. ; 12:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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| 24. |
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| 25. |
- Askling, J., et al.
(author)
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How comparable are rates of malignancies in patients with rheumatoid arthritis across the world? A comparison of cancer rates, and means to optimise their comparability, in five RA registries
- 2016
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 75:10, s. 1789-1796
-
Journal article (peer-reviewed)abstract
- Background The overall incidence of cancer in patients with rheumatoid arthritis (RA) is modestly elevated. The extent to which cancer rates in RA vary across clinical cohorts and patient subsets, as defined by disease activity or treatment is less known but critical for understanding the safety of existing and new antirheumatic therapies. We investigated comparability of, and means to harmonise, malignancy rates in five RA registries from four continents. Methods Participating RA registries were Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (several countries) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data, and sensitivity analyses of sub-cohorts defined by disease activity, treatment change, prior comorbidities and restricted by calendar time or follow-up, respectively. Malignancy rates with 95% CIs were estimated, and standardised for age and sex, based on the distributions from a typical RA clinical trial programme population (fostamatinib). Results There was a high consistency in rates for overall malignancy excluding non-melanoma skin cancer (NMSC), for malignant lymphomas, but not for all skin cancers, across registries, in particular following age/sex standardisation. Standardised rates of overall malignancy excluding NMSC varied from 0.56 to 0.87 per 100 person-years. Within each registry, rates were generally consistent across sensitivity analyses, which differed little from the main analysis. Conclusion In real-world RA populations, rates of both overall malignancy and of lymphomas are consistent.
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| 26. |
- Chong, K. Y., et al.
(author)
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A core outcome set for future research in ectopic pregnancy: an international consensus development study
- 2023
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In: Fertility and Sterility. - : Elsevier BV. - 0015-0282. ; 119:5, s. 804-812
-
Journal article (peer-reviewed)abstract
- Objective: To address methodological deficiencies in published randomized controlled trials and systematic reviews, this study has developed a core outcome set to guide future research in ectopic pregnancy (EP).Design: To identify potential outcomes, we performed a comprehensive literature review and interviews with individuals with lived experience in EP. Potential core outcomes were then entered into a 3-round Delphi survey. A total of 154 participants from 6 continents, comprising health care professionals, researchers, and individuals with lived experience in EP, completed all 3 rounds of the Delphi survey. Outcomes were prioritized at 3 consensus development meetings, and recommendations were developed on how to report these outcomes where possible.Setting: Not applicable.Patient(s): Health care professionals, researchers, and individuals with lived experience in EP.Intervention(s): Not applicable.Main Outcome Measure(s): Consensus for inclusion in core outcome set.Result(s): Six outcomes reached full consensus, including treatment success, resolution time, the number of additional interventions, adverse events, mortality and severe morbidity, and treatment satisfaction.Conclusion(s): The core outcome set with 6 outcomes for EP will help standardize reporting of clinical trials, facilitate implementation of findings into clinical practice, and enhance patient-centered care. (Fertil Sterile 2023;119:804-12. (c) 2023 by American Society for Reproductive Medicine.) El resumen esta disponible en Espanol al final del articulo.
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| 27. |
- Chong, K. Y., et al.
(author)
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A protocol for developing a core outcome set for ectopic pregnancy
- 2021
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In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 22:1
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Journal article (peer-reviewed)abstract
- Background: Randomised controlled trials (RCTs) evaluating ectopic pregnancy have reported many different outcomes, which are themselves often defined and measured in distinct ways. This level of variation results in an inability to compare results of individual RCTs. The development of a core outcome set to ensure outcomes important to key stakeholders are collected consistently will guide future research in ectopic pregnancy. Study aim: To develop and implement a core outcome set to guide future research in ectopic pregnancy. Methods and analysis: We have established an international steering group of key stakeholders, including healthcare professionals, researchers, and individuals with lived experience of ectopic pregnancy. We will identify potential outcomes from ectopic pregnancy from a comprehensive literature review of published randomised controlled trials. We will then utilise a modified Delphi method to prioritise outcomes. Subsequently, key stakeholders will be invited to score potential core outcomes on a nine-point Likert scale, ranging from 1 (not important) to 9 (critical). Repeated reflection and rescoring should promote whole and individual stakeholder group convergence towards consensus 'core' outcomes. We will also establish standardised definitions and recommend high-quality measurements for individual core outcomes.
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| 28. |
- Danese, E., et al.
(author)
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Impact of the CYP4F2 p.V433M Polymorphism on Coumarin Dose Requirement: Systematic Review and Meta-Analysis
- 2012
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In: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 1532-6535 .- 0009-9236. ; 92:6, s. 746-756
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Research review (peer-reviewed)abstract
- A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I-2 = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to coumarin drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms.
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| 29. |
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| 30. |
- Jordanova, V. K., et al.
(author)
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Specification of the near-Earth space environment with SHIELDS
- 2018
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In: Journal of Atmospheric and Solar-Terrestrial Physics. - : PERGAMON-ELSEVIER SCIENCE LTD. - 1364-6826 .- 1879-1824. ; 177, s. 148-159
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Journal article (peer-reviewed)abstract
- Predicting variations in the near-Earth space environment that can lead to spacecraft damage and failure is one example of "space weather" and a big space physics challenge. A project recently funded through the Los Alamos National Laboratory (LANL) Directed Research and Development (LDRD) program aims at developing a new capability to understand, model, and predict Space Hazards Induced near Earth by Large Dynamic Storms, the SHIELDS framework. The project goals are to understand the dynamics of the surface charging environment (SCE), the hot (keV) electrons representing the source and seed populations for the radiation belts, on both macro and micro-scale. Important physics questions related to particle injection and acceleration associated with magnetospheric storms and substorms, as well as plasma waves, are investigated. These challenging problems are addressed using a team of world-class experts in the fields of space science and computational plasma physics, and state-of-the-art models and computational facilities. A full two-way coupling of physics-based models across multiple scales, including a global MHD (BATS-R-US) embedding a particle-in-cell (iPIC3D) and an inner magnetosphere (RAM-SCB) codes, is achieved. New data assimilation techniques employing in situ satellite data are developed; these provide an order of magnitude improvement in the accuracy in the simulation of the SCE. SHIELDS also includes a post-processing tool designed to calculate the surface charging for specific spacecraft geometry using the Curvilinear Particle-In-Cell (CPIC) code that can be used for reanalysis of satellite failures or for satellite design.
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| 31. |
- Michaud, K., et al.
(author)
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Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease
- 2016
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 75:10, s. 1797-1805
-
Journal article (peer-reviewed)abstract
- Background We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality. Methods Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions. Rates were standardised for age, sex and, in one sensitivity analysis, also HAQ. Results The combined registry cohorts included 57251 patients with RA (234089 person-years)24.5% men, mean (SD) baseline age 58.2 (13.8) and RA duration 8.2 (11.7) years. Standardised registry mortality rates (per 100 person-years) varied from 0.42 (CORRONA) to 0.80 (NOAR), with 0.60 for RCT patients. Myocardial infarction and major adverse cardiovascular events (MACE) rates ranged from 0.09 and 0.31 (IORRA) to 0.39 and 0.77 (SRR), with RCT rates intermediate (0.18 and 0.42), respectively. Additional subcohort analyses showed small and mostly consistent changes across registries, retaining reasonable consistency in rates across the Western registries. Additional standardisation for HAQ returned higher mortality and MACE registry rates. Conclusions This coordinated approach to contextualising RA RCT safety data demonstrated reasonable differences and consistency in rates for mortality and CVD across registries, and comparable RCT rates, and may serve as a model method to supplement clinical trial analyses for drug development programmes.
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| 32. |
- Nyberg, Fredrik, 1961, et al.
(author)
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Comorbidity Burden in Trial-Aligned Patients with Established Gout in Germany, UK, US, and France: a Retrospective Analysis
- 2016
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In: Advances in Therapy. - : Springer Science and Business Media LLC. - 0741-238X .- 1865-8652. ; 33:7, s. 1180-1198
-
Journal article (peer-reviewed)abstract
- Patients with gout have numerous comorbidities. We aimed to estimate the prevalence and incidence rates of renal and cardiovascular morbidities in trial-aligned patients with established gout in Germany (DE), the United Kingdom (UK), the United States (US), and France (FR). This longitudinal cohort study used retrospective data from IMS Disease Analyzer (TM) (DE, FR), Clinical Practice Research Datalink-Hospital Episode Statistics (UK), and IMS' PharMetrics Plus database linked with outpatient laboratory results (US). Included patients were a parts per thousand yen18 years at index date (January 1, 2010; all dates +1 year for FR), with continuous enrollment during the pre-index year, had "prevalent established gout" determined by data in the pre-index year, and a parts per thousand yen1 documented visit after index date; additional inclusion/exclusion criteria were aligned with recent gout clinical trials. Look-back for comorbidity prevalence extended to January 1, 2003 (US: January 1, 2009). Follow-up for incidence extended from index date to at most March 26, 2013 (FR: May 31, 2014). Events of interest were identified by diagnostic codes and/or laboratory data. The trial-aligned cohorts included 35,118 (DE), 24,607 (UK), 121,591 (US), and 17,338 (FR) patients. Among renal conditions, baseline diagnosis of chronic kidney disease/renal failure was most prevalent in the UK followed by DE; abnormal serum creatinine was most prevalent in the UK. Hypertension was the most prevalent cardiovascular diagnosis in all countries, followed by ischemic heart disease (IHD) and myocardial infarction. Incidence rates (per 100 patient-years) for new/worsening renal impairment ranged from 1.67 (DE) to 4.34 (US) and for nephrolithiasis diagnosis from 0.31 (FR) to 3.79 (US). The incidence rates for hypertension diagnosis were highest among cardiovascular-related events, ranging from 3.23 (UK) to 20.27 (US), followed by IHD. Patients with established gout such as those included in gout trials have a high burden of established morbidity and new diagnoses of morbid events. Consideration of comorbidities, which greatly exacerbate disease burden, is important in gout management.
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| 33. |
- Nyberg, Fredrik, 1961, et al.
(author)
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Using epidemiological registry data to provide background rates as context for adverse events in a rheumatoid arthritis drug development program: a coordinated approach
- 2015
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In: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 24:11, s. 1121-1132
-
Journal article (peer-reviewed)abstract
- Purpose Observational studies can provide context for adverse events observed in clinical trials, especially for infrequent events or long-term risks. We developed methods to improve safety contextualization for a rheumatoid arthritis drug development program through coordinated analyses of multiple registries. Methods We identified and characterized differences and similarities across five registries (Swedish Rheumatology Quality of Care Register, Consortium of Rheumatology Researchers of North America [CORRONA], Norfolk Arthritis Register, Institute of Rheumatology Rheumatoid Arthritis, and the new CORRONA International), harmonized outcome definitions, and investigated whether restricted subcohorts improved comparability with trial populations. To address confounding, we identified risk predictors for outcomes of interest (mortality, cardiovascular disease, infection, and malignancy). We used patient-level analyses at each registry and central analysis of standardized group-level data. Results Despite data differences, the coordinated approach enabled consistent variable definitions for key baseline characteristics and outcomes. Selection of restricted subcohorts (e.g., using active joint count criteria) improved baseline comparability with trial patients for some rheumatoid arthritis disease activity measures, but less for other characteristics (e.g., age and comorbidity); however, such selection decreased sample size considerably. For most outcomes, age was the most important risk predictor, emphasizing the importance of age/sex standardization to address confounding. The prospective approach enabled use of recent relevant data; the distributed analysis safeguarded confidentiality of registry data. Conclusions Compared with reliance on published data alone, a forward-looking coordinated approach across multiple observational data sources can improve comparability and consistency and better support sensitivity analyses and data interpretation, in contextualizing safety data from clinical trials. This approach may have utility to support safety assessments across diverse diseases and drug development programs and satisfy future regulatory requirements. Copyright (C) 2015 John Wiley & Sons, Ltd.
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| 34. |
- Persson, Carina, 1964, et al.
(author)
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TOI-2196 b: Rare planet in the hot Neptune desert transiting a G-type star
- 2022
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
-
Journal article (peer-reviewed)abstract
- The hot Neptune desert is a region hosting a small number of short-period Neptunes in the radius-instellation diagram. Highly irradiated planets are usually either small (R less than or similar to 2 R-circle plus) and rocky or they are gas giants with radii of greater than or similar to 1 R-J. Here, we report on the intermediate-sized planet TOI-2196 b (TIC 372172128.01) on a 1.2 day orbit around a G-type star (V = 12.0, [Fe/H] = 0.14 dex) discovered by the Transiting Exoplanet Survey Satellite in sector 27. We collected 41 radial velocity measurements with the HARPS spectrograph to confirm the planetary nature of the transit signal and to determine the mass. The radius of TOI-2196 b is 3.51 +/- 0.15 R-circle plus, which, combined with the mass of 26.0 +/- 1.3 M-circle plus, results in a bulk density of 3.31(-0.43)(+0.51) g cm(-3). Hence, the radius implies that this planet is a sub-Neptune, although the density is twice than that of Neptune. A significant trend in the HARPS radial velocity measurements points to the presence of a distant companion with a lower limit on the period and mass of 220 days and 0.65 M-J, respectively, assuming zero eccentricity. The short period of planet b implies a high equilibrium temperature of 1860 +/- 20 K, for zero albedo and isotropic emission. This places the planet in the hot Neptune desert, joining a group of very few planets in this parameter space discovered in recent years. These planets suggest that the hot Neptune desert may be divided in two parts for planets with equilibrium temperatures of greater than or similar to 1800 K: a hot sub-Neptune desert devoid of planets with radii of approximate to 1.8-3 R-circle plus and a sub-Jovian desert for radii of approximate to 5-12 R-circle plus. More planets in this parameter space are needed to further investigate this finding. Planetary interior structure models of TOI-2196 b are consistent with a H/He atmosphere mass fraction between 0.4% and 3%, with a mean value of 0.7% on top of a rocky interior. We estimated the amount of mass this planet might have lost at a young age and we find that while the mass loss could have been significant, the planet had not changed in terms of character: it was born as a small volatile-rich planet and it remains one at present.
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Short, P., et al.
(author)
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The tidal disruption event AT2018hyz-I. Double-peaked emission lines and a flat Balmer decrement
- 2020
-
In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 498:3, s. 4119-4133
-
Journal article (peer-reviewed)abstract
- We present results from spectroscopic observations of AT 2018hyz, a transient discovered by the All-Sky Automated Survey for Supernova survey at an absolute magnitude of M-V similar to -20.2 mag, in the nucleus of a quiescent galaxy with strong Balmer absorption lines. AT 2018hyz shows a blue spectral continuum and broad emission lines, consistent with previous TDE candidates. High cadence follow-up spectra show broad Balmer lines and He I in early spectra, with He II making an appearance after similar to 70-100 d. The Balmer lines evolve from a smooth broad profile, through a boxy, asymmetric double-peaked phase consistent with accretion disc emission, and back to smooth at late times. The Balmer lines are unlike typical active galactic nucleus in that they show a flat Balmer decrement (H alpha/H beta similar to 1.5), suggesting the lines are collisionally excited rather than being produced via photoionization. The flat Balmer decrement together with the complex profiles suggests that the emission lines originate in a disc chromosphere, analogous to those seen in cataclysmic variables. The low optical depth of material due to a possible partial disruption may be what allows us to observe these double-peaked, collisionally excited lines. The late appearance of He II may be due to an expanding photosphere or outflow, or late-time shocks in debris collisions.
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| 39. |
- Simpson, E. K., et al.
(author)
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Independent Discovery of the Transiting Exoplanet HAT-P-14b
- 2011
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In: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 141:5, s. 161-
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Journal article (peer-reviewed)abstract
- We present SuperWASP observations of HAT-P-14b, a hot Jupiter discovered by Torres et al. The planet was found independently by the SuperWASP team and named WASP-27b after follow-up observations had secured the discovery, but prior to the publication by Torres et al. Our analysis of HAT-P-14/WASP-27 is in good agreement with the values found by Torres et al. and we provide additional evidence against astronomical false positives. Due to the brightness of the host star, V-mag = 10, HAT-P-14b is an attractive candidate for further characterization observations. The planet has a high impact parameter and the primary transit is close to grazing. This could readily reveal small deviations in the orbital parameters indicating the presence of a third body in the system, which may be causing the small but significant orbital eccentricity. Our results suggest that the planet may undergo a grazing secondary eclipse. However, even a non-detection would tightly constrain the system parameters.
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| 40. |
- Simpson, E. K., et al.
(author)
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WASP-37b : A 1.8 MJ exoplanet transiting a metal-poor star
- 2011
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In: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 141:1, s. 8-
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Journal article (peer-reviewed)abstract
- We report on the discovery of WASP-37b, a transiting hot Jupiter orbiting an m(v) = 12.7 G2-type dwarf, with a period of 3.577469 +/- 0.000011 d, transit epoch T-0 = 2455338.6188 +/- 0.0006 (HJD; dates throughout the paper are given in Coordinated Universal Time (UTC)), and a transit duration 0.1304(-0.0017)(+0.0018) d. The planetary companion has a mass M-p = 1.80 +/- 0.17 M-J and radius R-p = 1.16(-0.06)(+0.07) R-J, yielding a mean density of 1.15(-0.15)(+0.12) rho(J). From a spectral analysis, we find that the host star has M-star = 0.925 +/- 0.120 M-circle dot, R-star = 1.003 +/- 0.053 R-circle dot, T-eff = 5800 +/- 150 K, and [Fe/H] = -0.40 +/- 0.12. WASP-37 is therefore one of the lowest metallicity stars to host a transiting planet.
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| 41. |
- Verstappen, S. M. M., et al.
(author)
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Methodological Challenges When Comparing Demographic and Clinical Characteristics of International Observational Registries
- 2015
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In: Arthritis Care & Research. - : Wiley. - 2151-464X .- 2151-4658. ; 67:12, s. 1637-1645
-
Journal article (peer-reviewed)abstract
- Objective. Comparisons of data from different registries can be helpful in understanding variations in many aspects of rheumatoid arthritis (RA). The study aim was to assess and improve the comparability of demographic, clinical, and comorbidity data from 5 international RA registries. Methods. Using predefined definitions, 2 subsets of patients (main cohort and subcohort) from 5 international observational registries (Consortium of Rheumatology Researchers of North America Registry [CORRONA], the Swedish Rheumatology Quality of Care Register [SRR], the Norfolk Arthritis Register [NOAR], the Institute of Rheumatology Rheumatoid Arthritis cohort [IORRA], and CORRONA International) were evaluated and compared. Patients ages >18 years with RA, and present in or recruited to the registry from January 1, 2000, were included in the main cohort. Patients from the main cohort with positive rheumatoid factor and/or erosive RA who had received >= 1 synthetic disease-modifying antirheumatic drug (DMARD), and switched to or added another DMARD, were included in the subcohort at time of treatment switch. Results. Age and sex distributions were fairly similar across the registries. The percentage of patients with a high Disease Activity Score in 28 joints score varied between main cohorts (17.5% IORRA, 18.9% CORRONA, 24.7% NOAR, 27.7% CORRONA International, and 36.8% SRR), with IORRA, CORRONA, and CORRONA International including more prevalent cases of RA; the differences were smaller for the subcohort. Prevalence of comorbidities varied across registries (e.g., coronary artery disease ranged from 1.5% in IORRA to 7.9% in SRR), partly due to the way comorbidity data were captured and general cultural differences; the pattern was similar for the subcohorts. Conclusion. Despite different inclusion criteria for the individual RA registries, it is possible to improve the comparability and interpretability of differences across RA registries by applying well-defined cohort definitions.
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| 42. |
- Abrahams, Harriët J. G., et al.
(author)
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Moderators of the effect of psychosocial interventions on fatigue in women with breast cancer and men with prostate cancer : Individual patient data meta-analyses
- 2020
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In: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 29:11, s. 1772-1785
-
Research review (peer-reviewed)abstract
- ObjectivePsychosocial interventions can reduce cancer‐related fatigue effectively. However, it is still unclear if intervention effects differ across subgroups of patients. These meta‐analyses aimed at evaluating moderator effects of (a) sociodemographic characteristics, (b) clinical characteristics, (c) baseline levels of fatigue and other symptoms, and (d) intervention‐related characteristics on the effect of psychosocial interventions on cancer‐related fatigue in patients with non‐metastatic breast and prostate cancer.MethodsData were retrieved from the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium. Potential moderators were studied with meta‐analyses of pooled individual patient data from 14 randomized controlled trials through linear mixed‐effects models with interaction tests. The analyses were conducted separately in patients with breast (n = 1091) and prostate cancer (n = 1008).ResultsStatistically significant, small overall effects of psychosocial interventions on fatigue were found (breast cancer: β = −0.19 [95% confidence interval (95%CI) = −0.30; −0.08]; prostate cancer: β = −0.11 [95%CI = −0.21; −0.00]). In both patient groups, intervention effects did not differ significantly by sociodemographic or clinical characteristics, nor by baseline levels of fatigue or pain. For intervention‐related moderators (only tested among women with breast cancer), statistically significant larger effects were found for cognitive behavioral therapy as intervention strategy (β = −0.27 [95%CI = −0.40; −0.15]), fatigue‐specific interventions (β = −0.48 [95%CI = −0.79; −0.18]), and interventions that only targeted patients with clinically relevant fatigue (β = −0.85 [95%CI = −1.40; −0.30]).ConclusionsOur findings did not provide evidence that any selected demographic or clinical characteristic, or baseline levels of fatigue or pain, moderated effects of psychosocial interventions on fatigue. A specific focus on decreasing fatigue seems beneficial for patients with breast cancer with clinically relevant fatigue.
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| 43. |
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| 44. |
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| 45. |
- Austin, James D, et al.
(author)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 February 2011-31 March 2011.
- 2011
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In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 11:4, s. 757-758
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Journal article (peer-reviewed)abstract
- This article documents the addition of 111 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Acipenser oxyrinchus desotoi, Anopheles nuneztovari sensu lato, Asellus aquaticus, Calopteryx splendens, Calopteryx virgo, Centaurea aspera, Centaurea seridis, Chilina dombeyana, Proctoeces cf. lintoni and Pyrenophora teres f. teres.
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| 46. |
- Bergsten, Elisabet, et al.
(author)
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Confirmed efficacy of etoposide and dexamethasone in HLH treatment : long-term results of the cooperative HLH-2004 study
- 2017
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:25, s. 2728-2738
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Journal article (peer-reviewed)abstract
- Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. In the HLH-94 study, with an estimated 5-year probability of survival (pSu) of 54% (95% confidence interval, 48%-60%), systemic therapy included etoposide, dexamethasone, and, from week 9, cyclosporine A (CSA). Hematopoietic stem cell transplantation (HSCT) was indicated in patients with familial/genetic, relapsing, or severe/persistent disease. In HLH-2004, CSA was instead administered upfront, aiming to reduce pre-HSCT mortality and morbidity. From 2004 to 2011, 369 children aged <18 years fulfilled HLH-2004 inclusion criteria (5 of 8 diagnostic criteria, affected siblings, and/or molecular diagnosis in FHL-causative genes). At median follow-up of 5.2 years, 230 of 369 patients (62%) were alive (5-year pSu, 61%; 56%-67%). Five-year pSu in children with (n = 168) and without (n = 201) family history/genetically verified FHL was 59% (52%-67%) and 64% (57%-71%), respectively (familial occurrence [n = 47], 58% [45%-75%]). Comparing with historical data (HLH-94), using HLH-94 inclusion criteria, pre-HSCT mortality was nonsignificantly reduced from 27% to 19% (P = .064 adjusted for age and sex). Time from start of therapy to HSCT was shorter compared with HLH-94 (P =020 adjusted for age and sex) and reported neurological alterations at HSCT were 22% in HLH-94 and 17% in HLH-2004 (using HLH-94 inclusion criteria). Five-year pSu post-HSCT overall was 66% (verified FHL, 70% [63%-78%]). Additional analyses provided specific suggestions on potential pre-HSCT treatment improvements. HLH-2004 confirms that a majority of patients may be rescued by the etoposide/dexamethasone combination but intensification with CSA upfront, adding corticosteroids to intrathecal therapy, and reduced time to HSCT did not improve outcome significantly.
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- Currie, M. J., et al.
(author)
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N-acetylmannosamine-6-phosphate 2-epimerase uses a novel substrate-assisted mechanism to catalyze amino sugar epimerization
- 2021
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In: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258 .- 1083-351X. ; 297:4
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Journal article (peer-reviewed)abstract
- There are five known general catalytic mechanisms used by enzymes to catalyze carbohydrate epimerization. The amino sugar epimerase N-acetylmannosamine-6-phosphate 2-epimerase (NanE) has been proposed to use a deprotonation-reprotonation mechanism, with an essential catalytic lysine required for both steps. However, the structural determinants of this mechanism are not clearly established. We characterized NanE from Staphylo-coccus aureus using a new coupled assay to monitor NanE catalysis in real time and found that it has kinetic constants comparable with other species. The crystal structure of NanE from Staphylo-coccus aureus, which comprises a triosephosphate isomerase barrel fold with an unusual dimeric architecture, was solved with both natural and modified substrates. Using these substrate-bound structures, we identified the following active-site residues lining the cleft at the C-terminal end of the beta-strands: Gln11, Arg40, Lys63, Asp124, Glu180, and Arg208, which were individually substituted and assessed in relation to the mechanism. From this, we re-evaluated the central role of Glu180 in this mechanism alongside the catalytic lysine. We observed that the substrate is bound in a conformation that ideally positions the C5 hydroxyl group to be activated by Glu180 and donate a proton to the C2 carbon. Taken together, we propose that NanE uses a novel substrate-assisted proton displacement mechanism to invert the C2 stereocenter of N-acetylmannosamine-6-phosphate. Our data and mechanistic interpretation may be useful in the development of inhibitors of this enzyme or in enzyme engineering to produce biocatalysts capable of changing the stereochemistry of molecules that are not amenable to synthetic methods.
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