| 1. |
- Walker, Logan C, et al.
(author)
-
Evidence for SMAD3 as a modifier of breast cancer risk in BRCA2 mutation carriers.
- 2010
-
In: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-542X .- 1465-5411. ; 12:6
-
Journal article (peer-reviewed)abstract
- Current attempts to identify genetic modifiers of BRCA1 and BRCA2 associated risk have focused on a candidate gene approach, based on knowledge of gene functions, or the development of large genome-wide association studies. In this study, we evaluated 24 SNPs tagged to 14 candidate genes derived through a novel approach that analysed gene expression differences to prioritise candidate modifier genes for association studies.
|
|
| 2. |
- Ahmad, Yousif, et al.
(author)
-
Determining the Predominant Lesion in Patients With Severe Aortic Stenosis and Coronary Stenoses : A Multicenter Study Using Intracoronary Pressure and Flow
- 2019
-
In: Circulation. Cardiovascular Interventions. - 1941-7632. ; 12:12
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Patients with severe aortic stenosis (AS) often have coronary artery disease. Both the aortic valve and the coronary disease influence the blood flow to the myocardium and its ability to respond to stress; leading to exertional symptoms. In this study, we aim to quantify the effect of severe AS on the coronary microcirculation and determine if this is influenced by any concomitant coronary disease. We then compare this to the effect of coronary stenoses on the coronary microcirculation. METHODS: Group 1: 55 patients with severe AS and intermediate coronary stenoses treated with transcatheter aortic valve implantation (TAVI) were included. Group 2: 85 patients with intermediate coronary stenoses and no AS treated with percutaneous coronary intervention were included. Coronary pressure and flow were measured at rest and during hyperemia in both groups, before and after TAVI (group 1) and before and after percutaneous coronary intervention (group 2). RESULTS: Microvascular resistance over the wave-free period of diastole increased significantly post-TAVI (pre-TAVI, 2.71±1.4 mm Hg·cm·s-1 versus post-TAVI 3.04±1.6 mm Hg·cm·s-1 [P=0.03]). Microvascular reserve over the wave-free period of diastole significantly improved post-TAVI (pre-TAVI 1.88±1.0 versus post-TAVI 2.09±0.8 [P=0.003]); this was independent of the severity of the underlying coronary stenosis. The change in microvascular resistance post-TAVI was equivalent to that produced by stenting a coronary lesion with an instantaneous wave-free ratio of ≤0.74. CONCLUSIONS: TAVI improves microcirculatory function regardless of the severity of underlying coronary disease. TAVI for severe AS produces a coronary hemodynamic improvement equivalent to the hemodynamic benefit of stenting coronary stenoses with instantaneous wave-free ratio values <0.74. Future trials of physiology-guided revascularization in severe AS may consider using this value to guide treatment of concomitant coronary artery disease.
|
|
| 3. |
- Brigham-Grette, Julie, et al.
(author)
-
Pliocene warmth, polar amplification, and stepped pleistocene cooling recorded in NE arctic russia
- 2013
-
In: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 340:6139, s. 1421-1427
-
Journal article (peer-reviewed)abstract
- Understanding the evolution of Arctic polar climate from the protracted warmth of the middle Pliocene into the earliest glacial cycles in the Northern Hemisphere has been hindered by the lack of continuous, highly resolved Arctic time series. Evidence from Lake El'gygytgyn, in northeast (NE) Arctic Russia, shows that 3.6 to 3.4 million years ago, summer temperatures were similar to 8 degrees C warmer than today, when the partial pressure of CO2 was similar to 400 parts per million. Multiproxy evidence suggests extreme warmth and polar amplification during the middle Pliocene, sudden stepped cooling events during the Pliocene-Pleistocene transition, and warmer than present Arctic summers until similar to 2.2 million years ago, after the onset of Northern Hemispheric glaciation. Our data are consistent with sea-level records and other proxies indicating that Arctic cooling was insufficient to support large-scale ice sheets until the early Pleistocene.
|
|
| 4. |
- Conti, David, V, et al.
(author)
-
Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
-
In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
-
Journal article (peer-reviewed)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
|
|
| 5. |
- Downey, Harriet, et al.
(author)
-
Training future generations to deliver evidence-based conservation and ecosystem management
- 2021
-
In: Ecological Solutions and Evidence. - : Wiley. - 2688-8319. ; 2:1
-
Research review (peer-reviewed)abstract
- 1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis.2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice.3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses.4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.
|
|
| 6. |
- Gaudet, Mia M., et al.
(author)
-
Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer
- 2010
-
In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
-
Journal article (peer-reviewed)abstract
- The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
|
|
| 7. |
- Gonzalez, Alejandra, et al.
(author)
-
Second release of the CoRe database of binary neutron star merger waveforms
- 2023
-
In: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 40:8
-
Journal article (peer-reviewed)abstract
- We present the second data release of gravitational waveforms from binary neutron star (BNS) merger simulations performed by the Computational Relativity (CoRE) collaboration. The current database consists of 254 different BNS configurations and a total of 590 individual numerical-relativity simulations using various grid resolutions. The released waveform data contain the strain and the Weyl curvature multipoles up to l = m = 4. They span a significant portion of the mass, mass-ratio, spin and eccentricity parameter space and include targeted configurations to the events GW170817 and GW190425. CoRE simulations are performed with 18 different equations of state, seven of which are finite temperature models, and three of which account for nonhadronic degrees of freedom. About half of the released data are computed with high-order hydrodynamics schemes for tens of orbits to merger; the other half is computed with advanced microphysics. We showcase a standard waveform error analysis and discuss the accuracy of the database in terms of faithfulness. We present ready-to-use fitting formulas for equation of state-insensitive relations at merger (e.g. merger frequency), luminosity peak, and post-merger spectrum.
|
|
| 8. |
|
|
| 9. |
- Malinauskaite, Laura, et al.
(author)
-
Connecting the dots : An interdisciplinary perspective on climate change effects on whales and whale watching in Skjálfandi Bay, Iceland
- 2022
-
In: Ocean and Coastal Management. - : Elsevier BV. - 0964-5691 .- 1873-524X. ; 226
-
Journal article (peer-reviewed)abstract
- The paper presents a synthesis of some of the interdisciplinary work from the ARCPATH project that focuses on the effects of climate change on Arctic social-ecological systems. It does so through the prism of whales and their recreational ecosystem services (ES). Whales present a group of species that are vulnerable to climate change and, at the same time, are central to the economies, cultures, and identities of many Arctic coastal communities. One such community is the town of Húsavík in Skjálfandi Bay, Iceland. The paper conducts an initial literature review to examine the effects of climate change on whales, globally, before using these findings and site-specific data from climate change modelling, whale observations from whale watching boats and whale watching trip records to investigate possible future impacts on whale watching in Skjálfandi Bay. The literature review identifies three categories of impacts on whales due to climate change, which concern changing distributions and migration, prey availability, and sea-ice and ocean temperature. Linear regression models identify statistically significant relationships between sea-surface temperatures (SST) and cetacean sightings for minke whales, blue whales and white-beaked-dolphins over the period 1995 to 2017. These species appear to have changed their usual feeding areas, and the results imply that further increases in SST are likely to further affect whale distributions. Future climate scenarios indicate that at least 2 °C of SST warming in Skjálfandi Bay up to 2050 might be inevitable regardless of the future emissions scenario, which implies nearly certain change that would require adaptation. The reliance of the local tourism sector on whale watching makes Húsavík vulnerable to the effects of climate change on whales. The results of this interdisciplinary inquiry emphasize the interconnectedness of different components of social-ecological systems and calls for adaptation planning that would enhance the resilience of local community to climate change and conservation measures that could enhance the protection of whales beyond the scope of the current whale sanctuary in Skjálfandi Bay.
|
|
| 10. |
- Pal, Gian, et al.
(author)
-
Genetic Testing in Parkinson's Disease.
- 2023
-
In: Movement Disorders. - 0885-3185 .- 1531-8257. ; 38:8, s. 1384-1396
-
Journal article (peer-reviewed)abstract
- Genetic testing for persons with Parkinson's disease is becoming increasingly common. Significant gains have been made regarding genetic testing methods, and testing is becoming more readily available in clinical, research, and direct-to-consumer settings. Although the potential utility of clinical testing is expanding, there are currently no proven gene-targeted therapies, but clinical trials are underway. Furthermore, genetic testing practices vary widely, as do knowledge and attitudes of relevant stakeholders. The specter of testing mandates financial, ethical, and physician engagement, and there is a need for guidelines to help navigate the myriad of challenges. However, to develop guidelines, gaps and controversies need to be clearly identified and analyzed. To this end, we first reviewed recent literature and subsequently identified gaps and controversies, some of which were partially addressed in the literature, but many of which are not well delineated or researched. Key gaps and controversies include: (1) Is genetic testing appropriate in symptomatic and asymptomatic individuals without medical actionability? (2) How, if at all, should testing vary based on ethnicity? (3) What are the long-term outcomes of consumer- and research-based genetic testing in presymptomatic PD? (4) What resources are needed for clinical genetic testing, and how is this impacted by models of care and cost-benefit considerations? Addressing these issues will help facilitate the development of consensus and guidelines regarding the approach and access to genetic testing and counseling. This is also needed to guide a multidisciplinary approach that accounts for cultural, geographic, and socioeconomic factors in developing testing guidelines. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
|
|
