| 1. |
- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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| 2. |
- Ryu, Y. -H., et al.
(author)
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OGLE-2016-BLG-1190Lb : The First Spitzer Bulge Planet Lies Near the Planet/Brown-dwarf Boundary
- 2018
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In: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 155:1
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Journal article (peer-reviewed)abstract
- We report the discovery of OGLE-2016-BLG-1190Lb, which is likely to be the first Spitzer microlensing planet in the Galactic bulge/ bar, an assignation that can be confirmed by two epochs of high-resolution imaging of the combined source-lens baseline object. The planet's mass, M-p = 13.4 +/- 0.9 M-J, places it right at the deuteriumburning limit, i. e., the conventional boundary between planets and brown dwarfs. Its existence raises the question of whether such objects are really planets (formed within the disks of their hosts) or failed stars (lowmass objects formed by gas fragmentation). This question may ultimately be addressed by comparing disk and bulge/bar planets, which is a goal of the Spitzer microlens program. The host is a G dwarf, M-host = 0.89. +/- 0.07 M-circle dot, and the planet has a semimajor axis a similar to 2.0 au. We use Kepler K2 Campaign 9 microlensing data to break the lens-mass degeneracy that generically impacts parallax solutions from Earth-Spitzer observations alone, which is the first successful application of this approach. The microlensing data, derived primarily from near-continuous, ultradense survey observations from OGLE, MOA, and three KMTNet telescopes, contain more orbital information than for any previous microlensing planet, but not quite enough to accurately specify the full orbit. However, these data do permit the first rigorous test of microlensing orbital-motion measurements, which are typically derived from data taken over < 1% of an orbital period.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Bauer, M., et al.
(author)
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Solar insolation in springtime influences age of onset of bipolar I disorder
- 2017
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In: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 136:6, s. 571-582
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Research review (peer-reviewed)abstract
- Objective: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. Method: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. Results: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). Conclusion: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.
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| 7. |
- Udalski, A., et al.
(author)
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OGLE-2017-BLG-1434Lb : Eighth q < 1 x 10(-4) Mass-Ratio Microlens Planet Confirms Turnover in Planet Mass-Ratio Function
- 2018
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In: Acta Astronomica. - 0001-5237. ; 68:1, s. 1-42
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Journal article (peer-reviewed)abstract
- We report the discovery of a cold Super-Earth planet (m(p) = 4.4 +/- 0.5 M-circle plus) orbiting a low-mass (M = 0.23 +/- 0.03 M-circle dot) M dwarf at projected separation a(perpendicular to) l = 1.18 +/- 0.10 a.u., i.e., about 1.9 times the distance the snow line. The system is quite nearby for a microlensing planet, D-L = 0.86 +/- 0.09 kpc. Indeed, it was the large lens-source relative parallax pi(rel) = 1.0 mas (combined with the low mass M) that gave rise to the large, and thus well-measured, microlens parallax pi(E) proportional to (pi(rel)/M)(1)(/2) that enabled these precise measurements. OGLE-2017-BLG-1434Lb is the eighth microlensing planet with planet-host mass ratio q < 1 x 10(-4). We apply a new planet-detection sensitivity method, which is a variant of V/V-max, to seven of these eight planets to derive the mass-ratio function in this regime. We find dN/ d lnq proportional to q(P) , with p =1.05(-0.68)(+0.78), which confirms the turnover in the mass function found by Suzuki et al. relative to the power law of opposite sign n = -0.93 +/- 0.13 at higher mass ratios q greater than or similar to 2 x 10(-4). We combine our result with that of Suzuki et al. to obtain p = 0.73(-0.34)(+0.42.)
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| 8. |
- Han, C., et al.
(author)
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OGLE-2017-BLG-0329L : A Microlensing Binary Characterized with Dramatically Enhanced Precision Using Data from Space-based Observations
- 2018
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 859:2
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Journal article (peer-reviewed)abstract
- Mass measurements of gravitational microlenses require one to determine the microlens parallax pE, but precise pE measurement, in many cases, is hampered due to the subtlety of the microlens-parallax signal combined with the difficulty of distinguishing the signal from those induced by other higher-order effects. In this work, we present the analysis of the binary-lens event OGLE-2017-BLG-0329, for which pi(E) is measured with a dramatically improved precision using additional data from space-based Spitzer observations. We find that while the parallax model based on the ground-based data cannot be distinguished from a zero-pi(E) model at the 2 sigma level, the addition of the Spitzer data enables us to identify two classes of solutions, each composed of a pair of solutions according to the well-known ecliptic degeneracy. It is found that the space-based data reduce the measurement uncertainties of the north and east components of the microlens-parallax vector pE by factors similar to 18 and similar to 4, respectively. With the measured microlens parallax combined with the angular Einstein radius measured from the resolved caustic crossings, we find that the lens is composed of a binary with component masses of either (M-1, M-2) similar to (1.1, 0.8) M-circle dot or similar to(0.4, 0.3) M-circle dot according to the two solution classes. The first solution is significantly favored but the second cannot be securely ruled out based on the microlensing data alone. However, the degeneracy can be resolved from adaptive optics observations taken similar to 10 years after the event.
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| 9. |
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| 10. |
- Gould, A., et al.
(author)
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MOA-2010-BLG-523:" Failed Planet"= RS CVn Star
- 2013
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In: Astrophysical Journal. - 0004-637X. ; 763:2
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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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| 11. |
- Graslund, S, et al.
(author)
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Protein production and purification
- 2008
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In: Nature methods. - : Springer Science and Business Media LLC. - 1548-7105 .- 1548-7091. ; 5:2, s. 135-146
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Journal article (peer-reviewed)
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| 12. |
- Kong, Wan-Yee, et al.
(author)
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Validation of Serial Alberta Stroke Program Early CT Score as an Outcome Predictor in Thrombolyzed Stroke Patients.
- 2017
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In: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057 .- 1532-8511. ; 26:10, s. 2264-2271
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Journal article (peer-reviewed)abstract
- BACKGROUND: The Alberta Stroke Program Early CT Score (ASPECTS) on baseline imaging is an established predictor of functional outcome in anterior circulation acute ischemic stroke (AIS). We studied ASPECTS before intravenous thrombolysis (IVT) and at 24 hours to assess its prognostic value.METHODS: Data for consecutive anterior circulation AIS patients treated with IVT from 2006 to 2013 were extracted from a prospectively managed registry at our tertiary center. Pre-thrombolysis and 24-hour ASPECTS were evaluated by 2 independent neuroradiologists. Outcome measures included symptomatic intracranial hemorrhage (SICH), modified Rankin Scale (mRS) at 90 days, and mortality. Unfavorable functional outcome was defined by mRS >1. Dramatic ASPECTS progression (DAP) was defined as deterioration in ASPECTS by 6 points or more.RESULTS: Of 554 AIS patients thrombolyzed during the study period, 400 suffered from anterior circulation infarction. The median age was 65 years (interquartile range (IQR): 59-70) and the median National Institutes of Health Stroke Scale score was 18 points (IQR: 12-22). Compared with the pre-IVT ASPECTS (area under the curve [AUC] = .64, 95% confidence interval [CI]: .54-.65, P = .001), ASPECTS on the 24-hour CT scan (AUC = .78, 95% CI: .73-.82, P < .001), and change in ASPECTS (AUC = .69, 95% CI: .64-.74, P < .001) were better predictors of unfavorable functional outcome at 3 months. DAP, noted in 34 (14.4%) patients with good baseline ASPECTS (8-10 points), was significantly associated with unfavorable functional outcome (odds ratio [OR]: 9.91, 95% CI: 3.37-29.19, P ≤ .001), mortality (OR: 21.99, 95% CI: 7.98-60.58, P < .001), and SICH (OR: 8.57, 95% CI: 2.87-25.59, P < .001).CONCLUSION: Compared with the pre-thrombolysis score, ASPECTS measured at 24 hours as well as serial change in ASPECTS is a better predictor of 3-month functional outcome.
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| 13. |
- Mahajan, Anubha, et al.
(author)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Journal article (peer-reviewed)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 14. |
- Bensby, T., et al.
(author)
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Chemical evolution of the Galactic bulge as traced by microlensed dwarf and subgiant stars : VI. Age and abundance structure of the stellar populations in the central sub-kpc of the Milky Way
- 2017
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 605
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Journal article (peer-reviewed)abstract
- We present a detailed elemental abundance study of 90 F and G dwarf, turn-off, and subgiant stars in the Galactic bulge. Based on high-resolution spectra acquired during gravitational microlensing events, stellar ages and abundances for 11 elements (Na, Mg, Al, Si, Ca, Ti, Cr, Fe, Zn, Y and Ba) have been determined. Four main findings are presented: (1) a wide metallicity distribution with distinct peaks at [Fe/H] = -1.09, -0.63, -0.20, + 0.12, + 0.41; (2) a highfraction of intermediate-age to young stars where at [Fe/H] > 0 more than 35% are younger than 8 Gyr, and for [Fe/H] ≲-0.5 most stars are 10 Gyr or older; (3) several episodes of significant star formation in the bulge has been identified: 3, 6, 8, and 11 Gyr ago; (4) tentatively the "knee" in the α-element abundance trends of the sub-solar metallicity bulge is located at a slightly higher [Fe/H] than in the local thick disk. These findings show that the Galactic bulge has complex age and abundance properties that appear to be tightly connected to the main Galactic stellar populations. In particular, the peaks in the metallicity distribution, the star formation episodes, and the abundance trends, show similarities with the properties of the Galactic thin and thick disks. At the same time, the star formation rate appears to have been slightly faster in the bulge than in the local thick disk, which most likely is an indication of the denser stellar environment closer to the Galactic centre. There are also additional components not seen outside the bulge region, and that most likely can be associated with the Galactic bar. Our results strengthen the observational evidence that support the idea of a secular origin for the Galactic bulge, formed out of the other main Galactic stellar populations present in the central regions of our Galaxy. Additionally, our analysis of this enlarged sample suggests that the (V-I)0 colour of the bulge red clump should be revised to 1.09.
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| 15. |
- Aimo, Alberto, et al.
(author)
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Cardiac remodelling - Part 2: Clinical, imaging and laboratory findings. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology
- 2022
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In: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:6, s. 944-958
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Research review (peer-reviewed)abstract
- In patients with heart failure, the beneficial effects of drug and device therapies counteract to some extent ongoing cardiac damage. According to the net balance between these two factors, cardiac geometry and function may improve (reverse remodelling, RR) and even completely normalize (remission), or vice versa progressively deteriorate (adverse remodelling, AR). RR or remission predict a better prognosis, while AR has been associated with worsening clinical status and outcomes. The remodelling process ultimately involves all cardiac chambers, but has been traditionally evaluated in terms of left ventricular volumes and ejection fraction. This is the second part of a review paper by the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology dedicated to ventricular remodelling. This document examines the proposed criteria to diagnose RR and AR, their prevalence and prognostic value, and the variables predicting remodelling in patients managed according to current guidelines. Much attention will be devoted to RR in patients with heart failure with reduced ejection fraction because most studies on cardiac remodelling focused on this setting.
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| 16. |
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| 17. |
- Bauer, Michael, et al.
(author)
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Association between solar insolation and a history of suicide attempts in bipolar I disorder.
- 2019
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In: Journal of psychiatric research. - : Elsevier BV. - 1879-1379 .- 0022-3956. ; 113, s. 1-9
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Journal article (peer-reviewed)abstract
- In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p<0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
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| 18. |
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| 19. |
- Dawson, K. S., et al.
(author)
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An Intensive Hubble Space Telescope Survey for z>1 Type Ia Supernovae by Targeting Galaxy Clusters
- 2009
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In: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 138, s. 1271-1283
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Journal article (peer-reviewed)abstract
- We present a new survey strategy to discover and study high-redshift Type Ia supernovae (SNe Ia) using the Hubble Space Telescope (HST). By targeting massive galaxy clusters at 0.9 < z < 1.5, we obtain a twofold improvement in the efficiency of finding SNe compared to an HST field survey and a factor of 3 improvement in the total yield of SN detections in relatively dust-free red-sequence galaxies. In total, sixteen SNe were discovered at z>0.95, nine of which were in galaxy clusters. This strategy provides an SN sample that can be used to decouple the effects of host-galaxy extinction and intrinsic color in high-redshift SNe, thereby reducing one of the largest systematic uncertainties in SN cosmology. Based on observations made with the NASA/ESA Hubble Space Telescope and obtained from the data archive at the Space Telescope Institute. STScI is operated by the Association of Universities for Research in Astronomy, Inc. under the NASA contract NAS 5-26555. The observations are associated with program 10496.
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| 20. |
- Flannick, Jason, et al.
(author)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Journal article (peer-reviewed)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 21. |
- Fuchsberger, Christian, et al.
(author)
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The genetic architecture of type 2 diabetes
- 2016
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Journal article (peer-reviewed)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 22. |
- Giacomini, K. M., et al.
(author)
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New and Emerging Research on Solute Carrier and ATP Binding Cassette Transporters in Drug Discovery and Development: Outlook from the International Transporter Consortium
- 2022
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In: Clinical Pharmacology & Therapeutics. - : Wiley. - 0009-9236 .- 1532-6535. ; 112:3, s. 540-561
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Journal article (peer-reviewed)abstract
- Enabled by a plethora of new technologies, research in membrane transporters has exploded in the past decade. The goal of this state-of-the-art article is to describe recent advances in research on membrane transporters that are particularly relevant to drug discovery and development. This review covers advances in basic, translational, and clinical research that has led to an increased understanding of membrane transporters at all levels. At the basic level, we describe the available crystal structures of membrane transporters in both the solute carrier (SLC) and ATP binding cassette superfamilies, which has been enabled by the development of cryogenic electron microscopy methods. Next, we describe new research on lysosomal and mitochondrial transporters as well as recently deorphaned transporters in the SLC superfamily. The translational section includes a summary of proteomic research, which has led to a quantitative understanding of transporter levels in various cell types and tissues and new methods to modulate transporter function, such as allosteric modulators and targeted protein degraders of transporters. The section ends with a review of the effect of the gut microbiome on modulation of transporter function followed by a presentation of 3D cell cultures, which may enable in vivo predictions of transporter function. In the clinical section, we describe new genomic and pharmacogenomic research, highlighting important polymorphisms in transporters that are clinically relevant to many drugs. Finally, we describe new clinical tools, which are becoming increasingly available to enable precision medicine, with the application of tissue-derived small extracellular vesicles and real-world biomarkers.
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| 23. |
- Gudbjartsson, Daniel F., et al.
(author)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
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Journal article (peer-reviewed)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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| 24. |
- Hirao, Yuki, et al.
(author)
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OGLE-2017-BLG-0406 : Spitzer Microlens Parallax Reveals Saturn-mass Planet Orbiting M-dwarf Host in the Inner Galactic Disk
- 2020
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In: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 160:2
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Journal article (peer-reviewed)abstract
- We report the discovery and analysis of the planetary microlensing event OGLE-2017-BLG-0406, which was observed both from the ground and by the Spitzer satellite in a solar orbit. At high magnification, the anomaly in the light curve was densely observed by ground-based-survey and follow-up groups, and it was found to be explained by a planetary lens with a planet/host mass ratio of q = 7.0 x 10(-4) from the light-curve modeling. The ground-only and Spitzer-only data each provide very strong one-dimensional (1D) constraints on the 2D microlens parallax vector pi(E). When combined, these yield a precise measurement of pi(E) and of the masses of the host M-host = 0.56 +/- 0.07 M-circle dot and planet M-planet = 0.41 +/- 0.05 M-Jup. The system lies at a distance D-L = 5.2 +/- 0.5 kpc from the Sun toward the Galactic bulge, and the host is more likely to be a disk population star according to the kinematics of the lens. The projected separation of the planet from the host is a(perpendicular to) = 3.5 +/- 0.3 au (i.e., just over twice the snow line). The Galactic-disk kinematics are established in part from a precise measurement of the source proper motion based on OGLE-IV data. By contrast, the Gaia proper-motion measurement of the source suffers from a catastrophic 10 sigma error.
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| 25. |
- Kokrashvili, Z, et al.
(author)
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Endocrine taste cells
- 2014
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In: The British journal of nutrition. - 1475-2662. ; 111111 Suppl 1, s. S23-S29
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Journal article (peer-reviewed)
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| 26. |
- Lawrenson, Kate, et al.
(author)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 27. |
- Levitis, E, et al.
(author)
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Centering inclusivity in the design of online conferences-An OHBM-Open Science perspective
- 2021
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In: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 10:8
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Journal article (peer-reviewed)abstract
- As the global health crisis unfolded, many academic conferences moved online in 2020. This move has been hailed as a positive step towards inclusivity in its attenuation of economic, physical, and legal barriers and effectively enabled many individuals from groups that have traditionally been underrepresented to join and participate. A number of studies have outlined how moving online made it possible to gather a more global community and has increased opportunities for individuals with various constraints, e.g., caregiving responsibilities.Yet, the mere existence of online conferences is no guarantee that everyone can attend and participate meaningfully. In fact, many elements of an online conference are still significant barriers to truly diverse participation: the tools used can be inaccessible for some individuals; the scheduling choices can favour some geographical locations; the set-up of the conference can provide more visibility to well-established researchers and reduce opportunities for early-career researchers. While acknowledging the benefits of an online setting, especially for individuals who have traditionally been underrepresented or excluded, we recognize that fostering social justice requires inclusivity to actively be centered in every aspect of online conference design.Here, we draw from the literature and from our own experiences to identify practices that purposefully encourage a diverse community to attend, participate in, and lead online conferences. Reflecting on how to design more inclusive online events is especially important as multiple scientific organizations have announced that they will continue offering an online version of their event when in-person conferences can resume.
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| 28. |
- Li, Josephine H., et al.
(author)
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Identification of Genetic Variation Influencing Metformin Response in a Multiancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP)
- 2023
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 72:8, s. 1161-1172
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Journal article (peer-reviewed)abstract
- Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been repli-cated in the Diabetes Prevention Program (DPP). To as-sess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (PBO; n = 887) arms. Multiple linear regression assessed association with 1-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal compo-nents. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes inci-dence. We identified four genome-wide significant variants after correcting for correlated traits (P < 9 × 1029). In the MET arm, rs144322333 near ENOSF1 (minor al-lele frequency [MAF]AFR = 0.07; MAFEUR = 0.002) was associated with an increase in percentage of glycated hemoglobin (per minor allele, b = 0.39 [95% CI 0.28, 0.50]; P = 2.8 × 10212). rs145591055 near OMSR (MAF = 0.10 in American Indians) was associated with weight loss (kilograms) (per G allele, b = 27.55 [95% CI 29.88, 25.22]; P = 3.2 × 10210) in the MET arm. Neither variant was significant in PBO; gene-by-treatment interaction was significant for both variants [P(G×T) < 1.0 × 1024 ]. Replication in individuals with diabetes did not yield significant findings. A GWAS for metformin response in prediabetes revealed novel ethnic-specific associations that require further investigation but may have implications for tailored therapy.
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| 29. |
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| 30. |
- Mueller, Stefanie H., et al.
(author)
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Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry
- 2023
-
In: Genome Medicine. - : BioMed Central (BMC). - 1756-994X. ; 15
-
Journal article (peer-reviewed)abstract
- Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
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| 31. |
- Rivard, Léna, et al.
(author)
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Atrial Fibrillation and Dementia : A Report From the AF-SCREEN International Collaboration
- 2022
-
In: Circulation. - 1524-4539. ; 145:5, s. 392-409
-
Research review (peer-reviewed)abstract
- Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.
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| 32. |
- Saeidi, Alireza, et al.
(author)
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Concurrent loss of co-stimulatory molecules and functional cytokine secretion attributes leads to proliferative senescence of CD8(+) T cells in HIV/TB co-infection
- 2015
-
In: Cellular Immunology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0008-8749 .- 1090-2163. ; 297:1, s. 19-32
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Journal article (peer-reviewed)abstract
- The role of T-cell immunosenescence and functional CD8(+) T-cell responses in HIV/TB co-infection is unclear. We examined and correlated surrogate markers of HIV disease progression with immune activation, immunosenescence and differentiation using T-cell pools of HIV/TB co-infected, HIV-infected and healthy controls. Our investigations showed increased plasma viremia and reduced CD4/CD8 T-cell ratio in HIV/TB co-infected subjects relative to HIV-infected, and also a closer association with changes in the expression of CD38, a cyclic ADP ribose hydrolase and CD57, which were consistently expressed on late-senescent CD8(+) T cells. Up-regulation of CD57 and CD38 were directly proportional to lack of co-stimulatory markers on CD8(+) T cells, besides diminished expression of CD127 (IL-7R alpha) on CD57(+)CD4(+) T cells. Notably, intracellular IFN-gamma, perforin and granzyme B levels in HIV-specific CD8(+) T cells of HIV/TB co-infected subjects were diminished. Intracellular CD57 levels in HIV gag p24-specific CD8(+) T cells were significantly increased in HIV/TB co-infection. We suggest that HIV-TB co-infection contributes to senescence associated with chronic immune activation, which could be due to functional insufficiency of CD8(+) T cells. (C) 2015 Elsevier Inc. All rights reserved.
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| 33. |
- Salvador, Christian Mark, 1989, et al.
(author)
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Assessment of Impact of Meteorology and Precursor in Long-term Trends of PM and Ozone in a Tropical City
- 2022
-
In: Aerosol and Air Quality Research. - : Taiwan Association for Aerosol Research. - 1680-8584 .- 2071-1409. ; 22:1
-
Journal article (peer-reviewed)abstract
- Long-term trends of atmospheric pollutants, particularly ozone (O-3) and particulate matter (PM) provide a direct evaluation of the response of the atmosphere to the environmental policies and the variability of anthropogenic and biogenic emissions. Here, we report the assessment of the temporal evolution of the air quality in a tropical urban city (Butuan) in the southern Philippines by evaluating the trends of meteorological conditions (i.e., temperature, R.H., boundary layer height), air pollutants (i.e., PM2.5, NO2, O-3) and their precursors (Benzene, Toluene, and Xylene) from 2014 to 2020. During the seven-year measurement, the mean PM2.5 and PM10 mass concentrations were 8.7 +/- 3.9 and 24.3 +/- 12.0 mu g m(-3), with no single day exceeded the daily PM limit. The max concentrations of aerosol occurred during the dry season when the loss of particles through wet deposition was limited. Speciation of PM2.5 indicated that fine aerosol was dominated by sea salt and organic matter (OM). Analysis of the ratio of OM and sulfate indicated that the main source of pollution in the city was wildfire/biomass burning. The average O-3 and NO2 mixing ratios during the same period were 22.3 +/- 9.5 ppb and 8.1 +/- 5.4 ppb while increasing at the rate of 0.409 ppb year(-1) and 0.683 ppb year(-1). The highest O-3 concentration occurred during the summer months when photochemistry enhanced the formation of tropospheric O-3. The increasing O-3 trend was attributed to the contribution of anthropogenic VOCs (AVOCs), based on their ozone-forming potentials (OFPs). The seven-year measurement also showcased the variability of the atmospheric pollutants during the COVID-19 pandemic of 2020, when O-3 substantially increased due to reduced vehicle transport activities. Overall, our results provide insights to better comprehend the sources of the variability of O-3 and PM on a long-term temporal scale, as well as implications on relevant environmental policies in controlling air pollutants in a tropical developing region.
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| 34. |
- Suzuki, N., et al.
(author)
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THE HUBBLE SPACE TELESCOPE CLUSTER SUPERNOVA SURVEY. V. IMPROVING THE DARK- ENERGY CONSTRAINTS ABOVE z > 1 AND BUILDING AN EARLY-TYPE-HOSTED SUPERNOVA SAMPLE
- 2012
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:1
-
Journal article (peer-reviewed)abstract
- We present Advanced Camera for Surveys, NICMOS, and Keck adaptive-optics-assisted photometry of 20 Type Ia supernovae (SNe Ia) from the Hubble Space Telescope (HST) Cluster Supernova Survey. The SNe Ia were discovered over the redshift interval 0.623 < z < 1.415. Of these SNe Ia, 14 pass our strict selection cuts and are used in combination with the world's sample of SNe Ia to derive the best current constraints on dark energy. Of our new SNe Ia, 10 are beyond redshift z = 1, thereby nearly doubling the statistical weight of HST-discovered SNe Ia beyond this redshift. Our detailed analysis corrects for the recently identified correlation between SN Ia luminosity and host galaxy mass and corrects the NICMOS zero point at the count rates appropriate for very distant SNe Ia. Adding these SNe improves the best combined constraint on dark-energy density,rho(DE)(z), at redshifts 1.0 < z < 1.6 by 18% (including systematic errors). For a flat. CDM universe, we find Omega(A) = 0.729 +/- 0.014 (68% confidence level (CL) including systematic errors). For a flat wCDM model, we measure a constant dark-energy equation-of-state parameter w = -1.013(-0.073)(+0.068) (68% CL). Curvature is constrained to similar to 0.7% in the owCDM model and to similar to 2% in a model in which dark energy is allowed to vary with parameters w(0) and w(a). Further tightening the constraints on the time evolution of dark energy will require several improvements, including high-quality multi-passband photometry of a sample of several dozenz > 1 SNe Ia. We describe how such a sample could be efficiently obtained by targeting cluster fields with WFC3 on board HST. The updated supernova Union2.1 compilation of 580 SNe is available at http://supernova.lbl.gov/Union.
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| 35. |
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| 36. |
- Theorell-Haglöw, Jenny, et al.
(author)
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Associations Between Obstructive Sleep Apnea and Measures of Arterial Stiffness
- 2019
-
In: Journal of Clinical Sleep Medicine (JCSM). - : AMER ACAD SLEEP MEDICINE. - 1550-9389 .- 1550-9397. ; 15:2, s. 201-206
-
Journal article (peer-reviewed)abstract
- Study Objectives: The aim of this study was to determine whether severity measures of obstructive sleep apnea (OSA) are associated with arterial stiffness and central blood pressure (two important cardiovascular risk factors) in a large group of patients with OSA. Methods: Baseline data from six studies on OSA in which arterial stiffness and central aortic blood pressure measures were determined using applanation tonometry were pooled. Associations between measures of arterial stiffness (heart rate corrected augmentation index [AI75]), central aortic blood pressure (central systolic pressure [CSP] and heart rate corrected central augmentation pressure [CAP75]) and measures of OSA severity were explored using stepwise regression modelling. Results: Data from 362 participants (M:F ratio 13:1) with mean (standard deviation) age 49.2 (11.0) years, body mass index 31.9 (5.3) kg/m(2), apnea-hypopnea index (AHI) 35.7 (20.7) events/h were included in the analyses. The AHI, oxygen desaturation index (ODI3%), and sleep time with SpO(2) < 90% (T90) were all associated with arterial stiffness (AI75), (AHI: adj. beta = .069; P = .01; ODI3%: adj. beta = .072; P = .01; T90: adj. beta = .18; P < .0001) and CAP75 (AHI: adj. beta = .030; P = .01; ODI3%: adj. beta = .027; P = .02; T90: adj. beta = .080; P < .0001). AHI was also associated with CSP (AHI: adj. beta = .11; P = .002). Conclusion: OSA severity was significantly associated with augmentation index and CAP75 although the relationships were not strong.
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| 37. |
- Theorell-Haglöw, Jenny, et al.
(author)
-
Changes of vitamin D levels and bone turnover markers after CPAP therapy : a randomized sham-controlled trial
- 2018
-
In: Journal of Sleep Research. - : WILEY. - 0962-1105 .- 1365-2869. ; 27:4
-
Journal article (peer-reviewed)abstract
- The aim was to investigate whether continuous positive airway pressure treatment could modulate serum vitamin D (25-hydroxyvitamin D) and bone turnover markers (collagen-type 1 cross-linked C-telopeptide, osteocalcin and N-terminal propeptide of type 1 collagen) in secondary analysis from a randomized controlled trial. Sixty-five continuous positive airway pressure-naive male patients with obstructive sleep apnea (age=49 +/- 12years, apnea-hypopnea index=39.9 +/- 17.7events h(-1), body mass index=31.3 +/- 5.2kgm(-2)) were randomized to receive either real (n=34) or sham (n=31) continuous positive airway pressure for 12weeks. At 12weeks, all participants received real continuous positive airway pressure for an additional 12weeks. After 12weeks of continuous positive airway pressure (real versus sham), there were nobetween-group differences for any of the main outcomes [25-hydroxyvitamin D: -0.80 +/- 5.28ngmL(-1) (mean +/- SE) versus 3.08 +/- 3.66ngmL(-1), P=0.42; collagen-type 1 cross-linked C-telopeptide: 0.011 +/- 0.014ngmL(-1) versus -0.004 +/- 0.009ngmL(-1), P=0.48; osteocalcin: 1.13 +/- 1.12ngmL(-1) versus 0.46 +/- 0.75ng mL(-1), P=0.80; N-terminal propeptide of type 1 collagen: 2.07 +/- 3.05gL(-1) versus -1.05 +/- 2.13gL(-1), P=0.48]. There were no further differences in subgroup analyses (continuous positive airway pressure-compliant patients, patients with severe obstructive sleep apnea or sleepy patients). However, after 24weeks irrespective of initial randomization, vitamin D increased in patients with severe obstructive sleep apnea (9.56 +/- 5.51ngmL(-1), P=0.045) and in sleepy patients (14.0 +/- 4.69ngmL(-1), P=0.007). Also, there was a significant increase in osteocalcin at 24weeks (3.27 +/- 1.06ngmL(-1), P=0.01) in compliant patients. We conclude that 12weeks of continuous positive airway pressure did not modulate vitamin D or modulate any of the bone turnover markers compared with sham. However, it is plausible that continuous positive airway pressure may have late beneficial effects on vitamin D levels and bone turnover markers in selected groups of patients with obstructive sleep apnea.
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| 38. |
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| 39. |
- Villforth, C., et al.
(author)
-
Variability and stability in blazar jets on time-scales of years : optical polarization monitoring of OJ 287 in 2005-2009
- 2010
-
In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 402:3, s. 2087-2111
-
Journal article (peer-reviewed)abstract
- OJ 287 is a BL Lac object at redshift z = 0.306 that has shown double-peaked bursts at regular intervals of similar to 12 yr during the last similar to 40 yr. We analyse optical photopolarimetric monitoring data from 2005 to 2009, during which the latest double-peaked outburst occurred. The aim of this study is twofold: firstly, we aim to analyse variability patterns and statistical properties of the optical polarization light curve. We find a strong preferred position angle in optical polarization. The preferred position angle can be explained by separating the jet emission into two components: an optical polarization core and chaotic jet emission. The optical polarization core is stable on time-scales of years and can be explained as emission from an underlying quiescent jet component. The chaotic jet emission sometimes exhibits a circular movement in the Stokes plane. We find six such events, all on the time-scales of 10-20 d. We interpret these events as a shock front moving forwards and backwards in the jet, swiping through a helical magnetic field. Secondly, we use our data to assess different binary black hole models proposed to explain the regularly appearing double-peaked bursts in OJ 287. We compose a list of requirements a model has to fulfil to explain the mysterious behaviour observed in OJ 287. The list includes not only characteristics of the light curve but also other properties of OJ 287, such as the black hole mass and restrictions on accretion flow properties. We rate all existing models using this list and conclude that none of the models is able to explain all observations. We discuss possible new explanations and propose a new approach to understanding OJ 287. We suggest that both the double-peaked bursts and the evolution of the optical polarization position angle could be explained as a sign of resonant accretion of magnetic field lines, a 'magnetic breathing' of the disc.
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| 40. |
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| 41. |
- Yap, Jane Yee, et al.
(author)
-
A graphical method for carbon dioxide emissions reduction in multi–product plants
- 2020
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In: Process Safety and Environmental Protection: Transactions of the Institution of Chemical Engineers, Part B. - : Elsevier BV. - 1744-3598 .- 0957-5820. ; 133, s. 51-63
-
Journal article (peer-reviewed)abstract
- Carbon dioxide emissions reduction has been a common trend for many industrial processes in recent years. However, few analytical tools have been developed for visualising CO2 emissions reduction and supporting decisions at the enterprise level. A graphical technique known as Carbon Emission Composite Curves was developed previously, but was limited to the production of single product. In this work, the CO2 emissions reduction procedure is focused and extended to multi-product plants, in which CO2 emissions of shared and dedicated facilities of the production line are analysed. For cases where the carbon intensity of shared facilities is higher than that of the dedicated facilities, CO2 emissions reduction should focus on the shared facilities, before efforts are put forward for the dedicated facilities. In contrast, when the carbon intensity of dedicated facilities is higher than that of the shared facilities, it is necessary to explore ways to reduce CO2 emissions of the dedicated facilities. Two case studies are used to illustrate the procedure.
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| 42. |
- Yap, Jane Yee, et al.
(author)
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A heuristic-based technique for carbon footprint reduction for the production of multiple products
- 2018
-
In: Chemical Engineering Transactions. - 2283-9216. ; 70, s. 943-948
-
Journal article (peer-reviewed)abstract
- Carbon footprint (CF) reduction is a common trend for many industrial processes in recent years. However, not many analytical tools have been developed for visualising CF reduction at enterprise level. A graphical technique known as the CF Composite Curves to aid decision making in CF reduction at enterprise level has been developed in previous work. However, the method was limited to the production of a single product. In this paper, the CF reduction procedure is extended to the more general case of multiple products. The CF of shared and independent facilities are analysed. An illustrative example shows that for cases when the CF intensity of shared facilities is higher than that of the independent facilities, CF reduction should focus on the shared facilities, before efforts are put forward for the independent facilities. In contrast, when the CF intensity of independent facilities is higher than that of the shared facilities, it is necessary to explore ways to reduce CF of the independent facilities.
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| 43. |
- Yasuda, Kazuki, et al.
(author)
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Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus
- 2008
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:9, s. 1092-1097
-
Journal article (peer-reviewed)abstract
- We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest P value (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.
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| 44. |
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| 45. |
- Yeo, Leonard L L, et al.
(author)
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Synchronous cardiocerebral infarction in the era of endovascular therapy : which to treat first?
- 2017
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In: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 44:1, s. 104-111
-
Journal article (peer-reviewed)abstract
- A cardiocerebral ischemic attack (CCI) or a concurrent acute ischemic stroke (AIS) and myocardial infarction (AMI) is a severe event with no clear recommendations for ideal management because of the rarity of the scenario. The narrow time window for treatment and complexity of the treatment decision puts immense pressure on the treating physician. We evaluated this challenging situation at our tertiary center. Using our prospective stroke database out of a total of 555 patients with acute ischemic stroke between 2009 and 2014, we identified five consecutive cases with CCI (incidence 0.009%). Demography, risk factor characteristics, vascular occlusions and treatment approach were recorded. Good functional outcome was defined by the modified Rankin scale (mRS) score of 0-2 points. Out of five patients, AIS was treated with endovascular treatment in three cases, while two were treated with intravenous thrombolysis only. One out of three patients had embolectomy of the brain performed prior to the coronary intervention, while the other two patients underwent coronary intervention first. One patient developed sudden cardiac arrest on day-2 and passed away. CCI is an uncommon and devastating clinical scenario, further research is needed for the ideal management strategy that provides the best outcomes. However, the rarity of the disease does not lend itself to the conduct of a trial easily. We have proposed a considered treatment algorithm based on the current literature and our experience.
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