| 1. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 2. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 3. |
- Mgongo, Melina Bernard, et al.
(författare)
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A Qualitative Study on Barriers to COVID-19 Vaccine Uptake among Community Members in Tanzania
- 2023
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Ingår i: Vaccines. - 2076-393X. ; 11:8, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- The use of vaccines is one of the key tools in reversing the COVID-19 pandemic; however, various reports reported the low uptake of the vaccines. This study explored the barriers to the COVID-19 vaccine uptake among community members in Tanzania. A qualitative explorative study was conducted in December 2021 and April 2022 in eight regions of Tanzania. Focus group discussions (FGDs) and in-depth interviews (IDIs) were the methods of data collection. A total of 48 FGDs and 32 IDIs were conducted. Participants were aware of the COVID-19 disease and vaccines. The barriers to the COVID-19 vaccine non-uptake included receiving contradicting statements from top government leaders, vaccine preceded the education, myths towards vaccines, the presence of different types of vaccines, the process of getting the vaccine, the influence of social media and random people from the community, and vaccine conflicting religious beliefs. Despite being aware of the vaccine, the uptake of the COVID-19 vaccine is still low. Interventions that focus on increasing community knowledge about COVID-19 vaccines and addressing myths about the vaccines are needed.
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| 4. |
- Rodrigues, Ian A., et al.
(författare)
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Defining a Minimum Set of Standardized Patient-centered Outcome Measures for Macular Degeneration
- 2016
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Ingår i: American Journal of Ophthalmology. - : Elsevier BV. - 0002-9394 .- 1879-1891. ; 168, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To define a minimum set of outcome measures for tracking, comparing, and improving macular degeneration care.DESIGN: Recommendations from a working group of international experts in macular degeneration outcomes registry development and patient advocates, facilitated by the International Consortium for Health Outcomes Measurement (ICHOM).METHODS: Modified Delphi technique, supported by structured teleconferences, followed by online surveys to drive consensus decisions. Potential outcomes were identified through literature review of outcomes collected in existing registries and reported in major clinical trials. Outcomes were refined by the working group and selected based on impact on patients, relationship to good clinical care, and feasibility of measurement in routine clinical practice.
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| 5. |
- Sederholm Lawesson, Sofia, 1973-, et al.
(författare)
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Association Between History of Adverse Pregnancy Outcomes and Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography.
- 2023
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 329:5, s. 393-404
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Tidskriftsartikel (refereegranskat)abstract
- Adverse pregnancy outcomes are recognized risk enhancers for cardiovascular disease, but the prevalence of subclinical coronary atherosclerosis after these conditions is unknown.To assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening.Cross-sectional study of a population-based cohort of women in Sweden (n=10528) with 1 or more deliveries in 1973 or later, ascertained via the Swedish National Medical Birth Register, who subsequently participated in the Swedish Cardiopulmonary Bioimage Study at age 50 to 65 (median, 57.3) years in 2013-2018. Delivery data were prospectively collected.Adverse pregnancy outcomes, including preeclampsia, gestational hypertension, preterm delivery, small-for-gestational-age infant, and gestational diabetes. The reference category included women with no history of these exposures.Coronary computed tomography angiography indexes, including any coronary atherosclerosis, significant stenosis, noncalcified plaque, segment involvement score of 4 or greater, and coronary artery calcium score greater than 100.A median 29.6 (IQR, 25.0-34.9) years after first registered delivery, 18.9% of women had a history of adverse pregnancy outcomes, with specific pregnancy histories ranging from 1.4% (gestational diabetes) to 9.5% (preterm delivery). The prevalence of any coronary atherosclerosis in women with a history of any adverse pregnancy outcome was 32.1% (95% CI, 30.0%-34.2%), which was significantly higher (prevalence difference, 3.8% [95% CI, 1.6%-6.1%]; prevalence ratio, 1.14 [95% CI, 1.06-1.22]) compared with reference women. History of gestational hypertension and preeclampsia were both significantly associated with higher and similar prevalence of all outcome indexes. For preeclampsia, the highest prevalence difference was observed for any coronary atherosclerosis (prevalence difference, 8.0% [95% CI, 3.7%-12.3%]; prevalence ratio, 1.28 [95% CI, 1.14-1.45]), and the highest prevalence ratio was observed for significant stenosis (prevalence difference, 3.1% [95% CI, 1.1%-5.1%]; prevalence ratio, 2.46 [95% CI, 1.65-3.67]). In adjusted models, odds ratios for preeclampsia ranged from 1.31 (95% CI, 1.07-1.61) for any coronary atherosclerosis to 2.21 (95% CI, 1.42-3.44) for significant stenosis. Similar associations were observed for history of preeclampsia or gestational hypertension among women with low predicted cardiovascular risk.Among Swedish women undergoing coronary computed tomography angiography screening, there was a statistically significant association between history of adverse pregnancy outcomes and image-identified coronary artery disease, including among women estimated to be at low cardiovascular disease risk. Further research is needed to understand the clinical importance of these associations.
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| 6. |
- Shrestha, Shakti R., Dr, et al.
(författare)
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Understanding the wider social and economic context of post-earthquake cordons : A comparative case study between Christchurch, Aotearoa (New Zealand) and L'Aquila, Italy
- 2022
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Ingår i: Earthquake spectra. - : Sage Publications. - 8755-2930 .- 1944-8201. ; 38:4, s. 2731-2753
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Tidskriftsartikel (refereegranskat)abstract
- Post-earthquake cordons have been used after seismic events around the world. However, there is limited understanding of cordons and how contextual information such as geography, sociocultural characteristics, economy, and institutional and governance structures affects decisions and operational procedures, including aspects related to spatial and temporal attributes of cordon establishment. This research aims to fill the gap in cordon knowledge through a qualitative comparative case study of two cities: Christchurch, New Zealand (Mw 6.2 earthquake, February 2011) and L’Aquila, Italy (Mw 6.3 earthquake, 2009). Both cities suffered comprehensive damage to their city centers and had cordons established for extended periods of time. Data collection was done through purposive and snowball sampling whereby 23 key informants were interviewed in total. Research participants held expert knowledge in their roles and responsibilities, that is, council members, emergency managers, politicians, business/insurance representatives, academics, and police. Results illustrate that cordons were primarily established to ensure safety of people and to maintain security. The extent and duration of the cordons were affected by the recovery approaches taken in respective cities, that is, in Christchurch demolition was widely undertaken which supported recovery and allowed for faster removal of cordons. In contrast, authorities in L’Aquila placed high value on heritage buildings which led to recovery strategy based on preserving and restoring most of the buildings which extended the duration of cordon. Extended cordons have many similarities but evolve overtime. This evolution of cordons is affected by site-specific needs; thus, cordons should be understood and planned based on contextual realities.
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| 7. |
- Shrestha, Shakti, Dr, et al.
(författare)
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To cordon or not to cordon : The inherent complexities of post-earthquake cordoning learned from Christchurch and Wellington experiences
- 2021
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Ingår i: Bulletin of the New Zealand Society for Earthquake Engineering. - : New Zealand Society for Earthquake Engineering. - 1174-9857 .- 2324-1543. ; 54:1, s. 40-48
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Tidskriftsartikel (refereegranskat)abstract
- The use of post-earthquake cordons as a tool to support emergency managers after an event has been documented around the world. However, there is limited research that attempts to understand the inherent complexities of cordoning once applied, particularly the longer-term impacts and consequences. This research aims to fill the gap by providing a detailed understanding of cordons, their management, and the implications of cordoning in a post-earthquake environment. We use a qualitative method to understand cordons through case studies of two cities where cordons were used at different temporal and spatial scales: Christchurch (M6.3, February 2011) and Wellington (M7.8 in Kaikōura, November 2016), New Zealand. Data was collected through 21 key informant interviews obtained through purposive and snowball sampling of participants who were directly or indirectly involved in a decision-making role and/or had influence in relation to the cordoning process. The participants were from varying backgrounds and roles i.e. emergency managers, council members, business representatives, insurance representatives, police, and communication managers. We find that cordons are used primarily as a tool to control access for the purpose of life safety and security, but cordons can also be adapted to support recovery. Broadly, our analysis suggests two key aspects, ‘decision-making’ and ‘operations and management’, which overlap and interact as part of a complex system. The underlying complexity arises in large part due to the multitude of sectors affected by cordons: economics, law, politics, governance, evacuation, civil liberties, available resources etc. The complexity further increases as the duration of cordoning is extended.
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| 8. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 9. |
- Tjernström, Michael, et al.
(författare)
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The Arctic Summer Cloud Ocean Study (ASCOS) : overview and experimental design
- 2014
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 14:6, s. 2823-2869
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Tidskriftsartikel (refereegranskat)abstract
- The climate in the Arctic is changing faster than anywhere else on earth. Poorly understood feedback processes relating to Arctic clouds and aerosol-cloud interactions contribute to a poor understanding of the present changes in the Arctic climate system, and also to a large spread in projections of future climate in the Arctic. The problem is exacerbated by the paucity of research-quality observations in the central Arctic. Improved formulations in climate models require such observations, which can only come from measurements in situ in this difficult-to-reach region with logistically demanding environmental conditions. The Arctic Summer Cloud Ocean Study (ASCOS) was the most extensive central Arctic Ocean expedition with an atmospheric focus during the International Polar Year (IPY) 2007-2008. ASCOS focused on the study of the formation and life cycle of low-level Arctic clouds. ASCOS departed from Longyearbyen on Svalbard on 2 August and returned on 9 September 2008. In transit into and out of the pack ice, four short research stations were undertaken in the Fram Strait: two in open water and two in the marginal ice zone. After traversing the pack ice northward, an ice camp was set up on 12 August at 87 degrees 21' N, 01 degrees 29' W and remained in operation through 1 September, drifting with the ice. During this time, extensive measurements were taken of atmospheric gas and particle chemistry and physics, mesoscale and boundary-layer meteorology, marine biology and chemistry, and upper ocean physics. ASCOS provides a unique interdisciplinary data set for development and testing of new hypotheses on cloud processes, their interactions with the sea ice and ocean and associated physical, chemical, and biological processes and interactions. For example, the first-ever quantitative observation of bubbles in Arctic leads, combined with the unique discovery of marine organic material, polymer gels with an origin in the ocean, inside cloud droplets suggests the possibility of primary marine organically derived cloud condensation nuclei in Arctic stratocumulus clouds. Direct observations of surface fluxes of aerosols could, however, not explain observed variability in aerosol concentrations, and the balance between local and remote aerosols sources remains open. Lack of cloud condensation nuclei (CCN) was at times a controlling factor in low-level cloud formation, and hence for the impact of clouds on the surface energy budget. ASCOS provided detailed measurements of the surface energy balance from late summer melt into the initial autumn freeze-up, and documented the effects of clouds and storms on the surface energy balance during this transition. In addition to such process-level studies, the unique, independent ASCOS data set can and is being used for validation of satellite retrievals, operational models, and reanalysis data sets.
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| 10. |
- Voyle, Nicola, et al.
(författare)
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Genetic Risk as a Marker of Amyloid-β and Tau Burden in Cerebrospinal Fluid
- 2017
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877. ; 55:4, s. 1417-1427
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Tidskriftsartikel (refereegranskat)abstract
- Background: The search for a biomarker of Alzheimer's disease (AD) pathology (amyloid-β (Aβ) and tau) is ongoing, with the best markers currently being measurements of Aβ and tau in cerebrospinal fluid (CSF) and via positron emission tomography (PET) scanning. These methods are relatively invasive, costly, and often have high screening failure rates. Consequently, research is aiming to elucidate blood biomarkers of Aβ and tau. Objective: This study aims to investigate a case/control polygenic risk score (PGRS) as a marker of tau and investigate blood markers of a combined Aβ and tau outcome for the first time. A sub-study also considers plasma tau as markers of Aβ and tau pathology in CSF. Methods: We used data from the EDAR∗, DESCRIPA∗∗, and Alzheimer's Disease Neuroimaging Initiative (ADNI) cohorts in a logistic regression analysis to investigate blood markers of Aβ and tau in CSF. In particular, we investigated the extent to which a case/control PGRS is predictive of CSF tau, CSF amyloid, and a combined amyloid and tau outcome. The predictive ability of models was compared to that of age, gender, and APOE genotype ('basic model'). Results: In EDAR and DESCRIPA test data, inclusion of a case/control PGRS was no more predictive of Aβ, and a combined Aβ and tau endpoint than the basic models (accuracies of 66.0, and 73.3 respectively). The tau model saw a small increase in accuracy compared to basic models (59.6%). ADNI 2 test data also showed a slight increase in accuracy for the Aβ model when compared to the basic models (61.4%). Conclusion: We see some evidence that a case/control PGRS is marginally more predictive of Aβ and tau pathology than the basic models. The search for predictive factors of Aβ and tau pathologies, above and beyond demographic information, is still ongoing. Better understanding of AD risk alleles, development of more sensitive assays, and studies of larger sample size are three avenues that may provide such factors. However, the clinical utility of possible predictors of brain Aβ and tau pathologies must also be investigated. ∗'Beta amyloid oligomers in the early diagnosis of AD and as marker for treatment response' ∗∗'Development of screening guidelines and criteria for pre-dementia Alzheimer's disease'.
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