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- Sweeney, M. D., et al.
(author)
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Vascular dysfunction-The disregarded partner of Alzheimer's disease
- 2019
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:1, s. 158-167
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Journal article (peer-reviewed)abstract
- Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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- Streatfield, P. Kim, et al.
(author)
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Malaria mortality in Africa and Asia : evidence from INDEPTH health and demographic surveillance system sites
- 2014
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In: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 7, s. 25369-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Malaria continues to be a major cause of infectious disease mortality in tropical regions. However, deaths from malaria are most often not individually documented, and as a result overall understanding of malaria epidemiology is inadequate. INDEPTH Network members maintain population surveillance in Health and Demographic Surveillance System sites across Africa and Asia, in which individual deaths are followed up with verbal autopsies.OBJECTIVE: To present patterns of malaria mortality determined by verbal autopsy from INDEPTH sites across Africa and Asia, comparing these findings with other relevant information on malaria in the same regions.DESIGN: From a database covering 111,910 deaths over 12,204,043 person-years in 22 sites, in which verbal autopsy data were handled according to the WHO 2012 standard and processed using the InterVA-4 model, over 6,000 deaths were attributed to malaria. The overall period covered was 1992-2012, but two-thirds of the observations related to 2006-2012. These deaths were analysed by site, time period, age group and sex to investigate epidemiological differences in malaria mortality.RESULTS: Rates of malaria mortality varied by 1:10,000 across the sites, with generally low rates in Asia (one site recording no malaria deaths over 0.5 million person-years) and some of the highest rates in West Africa (Nouna, Burkina Faso: 2.47 per 1,000 person-years). Childhood malaria mortality rates were strongly correlated with Malaria Atlas Project estimates of Plasmodium falciparum parasite rates for the same locations. Adult malaria mortality rates, while lower than corresponding childhood rates, were strongly correlated with childhood rates at the site level.CONCLUSIONS: The wide variations observed in malaria mortality, which were nevertheless consistent with various other estimates, suggest that population-based registration of deaths using verbal autopsy is a useful approach to understanding the details of malaria epidemiology.
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- Buena-Atienza, E, et al.
(author)
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De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy
- 2016
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 28253-
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Journal article (peer-reviewed)abstract
- X-linked cone dysfunction disorders such as Blue Cone Monochromacy and X-linked Cone Dystrophy are characterized by complete loss (of) or reduced L- and M- cone function due to defects in the OPN1LW/OPN1MW gene cluster. Here we investigated 24 affected males from 16 families with either a structurally intact gene cluster or at least one intact single (hybrid) gene but harbouring rare combinations of common SNPs in exon 3 in single or multiple OPN1LW and OPN1MW gene copies. We assessed twelve different OPN1LW/MW exon 3 haplotypes by semi-quantitative minigene splicing assay. Nine haplotypes resulted in aberrant splicing of ≥20% of transcripts including the known pathogenic haplotypes (i.e. ‘LIAVA’, ‘LVAVA’) with absent or minute amounts of correctly spliced transcripts, respectively. De novo formation of the ‘LIAVA’ haplotype derived from an ancestral less deleterious ‘LIAVS’ haplotype was observed in one family with strikingly different phenotypes among affected family members. We could establish intrachromosomal gene conversion in the male germline as underlying mechanism. Gene conversion in the OPN1LW/OPN1MW genes has been postulated, however, we are first to demonstrate a de novo gene conversion within the lineage of a pedigree.
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- Keeler, Bonnie L., et al.
(author)
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Social-ecological and technological factors moderate the value of urban nature
- 2019
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In: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 2:1, s. 29-38
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Research review (peer-reviewed)abstract
- Urban nature has the potential to improve air and water quality, mitigate flooding, enhance physical and mental health, and promote social and cultural well-being. However, the value of urban ecosystem services remains highly uncertain, especially across the diverse social, ecological and technological contexts represented in cities around the world. We review and synthesize research on the contextual factors that moderate the value and equitable distribution of ten of the most commonly cited urban ecosystem services. Our work helps to identify strategies to more efficiently, effectively and equitably implement nature-based solutions.
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- Kramer, Lilith, et al.
(author)
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New paths for modelling freshwater nature futures
- 2023
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In: Sustainability Science. - 1862-4065 .- 1862-4057.
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Journal article (peer-reviewed)abstract
- Freshwater ecosystems are exceptionally rich in biodiversity and provide essential benefits to people. Yet they are disproportionately threatened compared to terrestrial and marine systems and remain underrepresented in the scenarios and models used for global environmental assessments. The Nature Futures Framework (NFF) has recently been proposed to advance the contribution of scenarios and models for environmental assessments. This framework places the diverse relationships between people and nature at its core, identifying three value perspectives as points of departure: Nature for Nature, Nature for Society, and Nature as Culture. We explore how the NFF may be implemented for improved assessment of freshwater ecosystems. First, we outline how the NFF and its main value perspectives can be translated to freshwater systems and explore what desirable freshwater futures would look like from each of the above perspectives. Second, we review scenario strategies and current models to examine how freshwater modelling can be linked to the NFF in terms of its aims and outcomes. In doing so, we also identify which aspects of the NFF framework are not yet captured in current freshwater models and suggest possible ways to bridge them. Our analysis provides future directions for a more holistic freshwater model and scenario development and demonstrates how society can benefit from freshwater modelling efforts that are integrated with the value-perspectives of the NFF.
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- Milgrom, C, et al.
(author)
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Metatarsal strains are sufficient to cause fatigue fracture during cyclic overloading
- 2002
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In: Foot & ankle international. - : SAGE Publications. - 1071-1007 .- 1944-7876. ; 23:3, s. 230-235
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Journal article (peer-reviewed)abstract
- Human in vivo tibial strains during vigorous walking have not been found to exceed 1200 microstrains. These values are below those found in ex vivo studies (>3000 microstrains) to cause cortical bone fatigue failure, suggesting that an intermediate bone remodeling response may be associated with tibial stress fractures. Metatarsal stress fractures, however, often develop before there is time for such a response to occur. Simultaneous in vivo axial strains were measured at the mid diaphysis of the second metatarsal and the tibia in two subjects. Peak axial metatarsal compression strains and strain rates were significantly higher than those of the tibia during treadmill walking and jogging both barefoot and with running shoes and during simple calisthenics. During barefoot treadmill walking metatarsal compression strains were greater than 2500 microstrains. During one- and two-leg vertical jumps and broad jumping, both metatarsal compression and tension strains were >3000 microstrains. Compression and tension strains in the metatarsus unlike those of the tibia may be sufficiently high even during moderate exertional activities to cause fatigue failure of bone secondary to the number of loading cycles without an intermediate bone remodeling response.
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- Remme, Roy P., et al.
(author)
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An ecosystem service perspective on urban nature, physical activity, and health
- 2021
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:22
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Journal article (peer-reviewed)abstract
- Nature underpins human well-being in critical ways, especially in health. Nature provides pollination of nutritious crops, purification of drinking water, protection from floods, and climate security, among other well-studied health benefits. A crucial, yet challenging, research frontier is clarifying how nature promotes physical activity for its many mental and physical health benefits, particularly in densely populated cities with scarce and dwindling access to nature. Here we frame this frontier by conceptually developing a spatial decision-support tool that shows where, how, and for whom urban nature promotes physical activity, to inform urban greening efforts and broader health assessments. We synthesize what is known, present a model framework, and detail the model steps and data needs that can yield generalizable spatial models and an effective tool for assessing the urban nature-physical activity relationship. Current knowledge supports an initial model that can distinguish broad trends and enrich urban planning, spatial policy, and public health decisions. New, iterative research and application will reveal the importance of different types of urban nature, the different subpopulations who will benefit from it, and nature's potential contribution to creating more equitable, green, livable cities with active inhabitants.
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| 12. |
- Streatfield, P. Kim, et al.
(author)
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Cause-specific childhood mortality in Africa and Asia : evidence from INDEPTH health and demographic surveillance system sites
- 2014
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In: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 7
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Journal article (peer-reviewed)abstract
- BACKGROUND: Childhood mortality, particularly in the first 5 years of life, is a major global concern and the target of Millennium Development Goal 4. Although the majority of childhood deaths occur in Africa and Asia, these are also the regions where such deaths are least likely to be registered. The INDEPTH Network works to alleviate this problem by collating detailed individual data from defined Health and Demographic Surveillance sites. By registering deaths and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available.OBJECTIVE: To present a description of cause-specific mortality rates and fractions over the first 15 years of life as documented by INDEPTH Network sites in sub-Saharan Africa and south-east Asia.DESIGN: All childhood deaths at INDEPTH sites are routinely registered and followed up with verbal autopsy (VA) interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provided person-time denominators for mortality rates. Cause-specific mortality rates and cause-specific mortality fractions are presented according to WHO 2012 VA cause groups for neonatal, infant, 1-4 year and 5-14 year age groups.RESULTS: A total of 28,751 childhood deaths were documented during 4,387,824 person-years over 18 sites. Infant mortality ranged from 11 to 78 per 1,000 live births, with under-5 mortality from 15 to 152 per 1,000 live births. Sites in Vietnam and Kenya accounted for the lowest and highest mortality rates reported.CONCLUSIONS: Many children continue to die from relatively preventable causes, particularly in areas with high rates of malaria and HIV/AIDS. Neonatal mortality persists at relatively high, and perhaps sometimes under-documented, rates. External causes of death are a significant childhood problem in some settings.
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