| 1. |
- Chami, Nathalie, et al.
(författare)
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Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits
- 2016
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 99:1, s. 8-21
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Tidskriftsartikel (refereegranskat)abstract
- Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 x 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 x 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 x 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 x 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 x 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.
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| 2. |
- Conrad, Sarah, et al.
(författare)
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Distribution of Fe isotopes in particles and colloids in the salinity gradient along the Lena River plume, Laptev Sea
- 2019
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Ingår i: Biogeosciences. - : European Geosciences Union (EGU). - 1726-4170 .- 1726-4189. ; 16:6, s. 1305-1319
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Tidskriftsartikel (refereegranskat)abstract
- Riverine Fe input is the primary Fe source for the ocean. This study is focused on the distribution of Fe along the Lena River freshwater plume in the Laptev Sea using samples from a 600 km long transect in front of the Lena River mouth. Separation of the particulate ( > 0.22 μm), colloidal (0.22 μm–1 kDa), and truly dissolved (< 1 kDa) fractions of Fe was carried out. The total Fe concentrations ranged from 0.2 to 57μM with Fe dominantly as particulate Fe. The loss of > 99% of particulate Fe and about 90% of the colloidal Fe was observed across the shelf, while the truly dissolved phase was almost constant across the Laptev Sea. Thus, the truly dissolved Fe could be an important source of bioavailable Fe for plankton in the central Arctic Ocean, together with the colloidal Fe. Fe-isotope analysis showed that the particulate phase and the sediment below the Lena River freshwater plume had negative δ56Fe values (relative to IRMM-14). The colloidal Fe phase showed negative δ56Fe values close to the river mouth (about -0.20 ‰) and positive δ56Fe values in the outermost stations (about +0.10 ‰). We suggest that the shelf zone acts as a sink for Fe particles and colloids with negative δ56Fe values, representing chemically reactive ferrihydrites. The positive δ56Fe values of the colloidal phase within the outer Lena River freshwater plume might represent Fe oxyhydroxides, which remain in the water column, and will be the predominant δ56Fe composition in the Arctic Ocean.
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| 3. |
- Ecke, Frauke, et al.
(författare)
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Seasonal shift of diet in bank voles explains trophic fate of anthropogenic osmium?
- 2018
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 624, s. 1634-1639
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Tidskriftsartikel (refereegranskat)abstract
- Diet shifts are common in mammals and birds, but little is known about how such shifts along the food web affect contaminant exposure. Voles are staple food for many mammalian and avian predators. There is therefore a risk of transfer of contaminants accumulated in voles within the food chain. Osmium is one of the rarest earth elements with osmium tetroxide (OsO4 ) as the most toxic vapor-phase airborne contaminant. Anthropogenic OsO4 accumulates in fruticose lichens that are important winter food of bank voles (Myodes glareolus). Here, we test if a) anthropogenic osmium accumulates in bank voles in winter, and b) accumulation rates and concentrations are lower in autumn when the species is mainly herbivorous. Our study, performed in a boreal forest impacted by anthropogenic osmium, supported the hypotheses for all studied tissues (kidney, liver, lung, muscle and spleen) in 50 studied bank voles. In autumn, osmium concentrations in bank voles were even partly similar to those in the graminivorous field vole (Microtus agrestis: n =3D 14). In autumn but not in late winter/early spring, osmium concentrations were generally negatively correlated with body weight and root length of the first mandible molar, i.e. proxies of bank vole age. Identified negative correlations between organ-to-body weight ratios and osmium concentrations in late winter/early spring indicate intoxication. Our results suggest unequal accumulation risk for predators feeding on different cohorts of bank voles.
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| 4. |
- Engström, Emma, 1982-, et al.
(författare)
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Applying spatial regression to evaluate risk factors for microbiological contamination of urban groundwater sources in Juba, South Sudan
- 2017
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Ingår i: Hydrogeology Journal. - : Springer Verlag. - 1431-2174 .- 1435-0157. ; 25:4, s. 1077-1091
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Tidskriftsartikel (refereegranskat)abstract
- This study developed methodology for statistically assessing groundwater contamination mechanisms. It focused on microbial water pollution in low-income regions. Risk factors for faecal contamination of groundwater-fed drinking-water sources were evaluated in a case study in Juba, South Sudan. The study was based on counts of thermotolerant coliforms in water samples from 129 sources, collected by the humanitarian aid organisation Médecins Sans Frontières in 2010. The factors included hydrogeological settings, land use and socio-economic characteristics. The results showed that the residuals of a conventional probit regression model had a significant positive spatial autocorrelation (Moran’s I = 3.05, I-stat = 9.28); therefore, a spatial model was developed that had better goodness-of-fit to the observations. The most significant factor in this model (p-value 0.005) was the distance from a water source to the nearest Tukul area, an area with informal settlements that lack sanitation services. It is thus recommended that future remediation and monitoring efforts in the city be concentrated in such low-income regions. The spatial model differed from the conventional approach: in contrast with the latter case, lowland topography was not significant at the 5% level, as the p-value was 0.074 in the spatial model and 0.040 in the traditional model. This study showed that statistical risk-factor assessments of groundwater contamination need to consider spatial interactions when the water sources are located close to each other. Future studies might further investigate the cut-off distance that reflects spatial autocorrelation. Particularly, these results advise research on urban groundwater quality. © 2016, The Author(s).
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| 5. |
- Engström, Emma, 1982-, et al.
(författare)
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Modeling bacterial attenuation in on-site wastewater treatment systems using the active region model and column-scale data
- 2015
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Ingår i: Environmental Earth Sciences. - : Springer Science and Business Media LLC. - 1866-6280 .- 1866-6299. ; 74:6, s. 4827-4837
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial attenuation in porous media is often higher in columns than in the field. This study investigates whether this inconsistency could be attributed to finger flow, as assessed by the active region model (ARM). It develops a numerical model of flow and transport of the fecal indicator Escherichia coli in a wastewater infiltration basin from the literature. Modeling was based on the traditional, uniform flow approach (Richard’s equation) as well as the ARM, representing finger flow. The uniform flow model resulted in flow rates that decreased rapidly with filter depth and an underestimation of the observed average relative effluent concentration by three orders of magnitude. With the ARM, the flow rates remained high throughout the filter, more consistently with observations, and the relative effluent concentration (0.018) was relatively accurate in reproducing the field result (0.025). Considering a range of removal rates derived from laboratory studies, the ARM consistently enabled more accurate and conservative assessments of the filter efficiency; thus, results indicated that the ARM provides a more relevant approach to bacterial transport in wastewater infiltration basins with sandy, unstructured soils.
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| 6. |
- Engström, Emma, 1982-
(författare)
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Predicting the transport of Escherichia coli to groundwater
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Groundwater contamination with pathogens poses a health risk worldwide. Predictive modeling could provide decision support for risk analysis in this context. This study therefore aimed to improve predictive modeling of the transport of Escherichia coli (E. coli) to groundwater. Primarily, it included a review of the state-of-the-art of the underlying process, influencing factors and modeling approaches that relate to E. coli transport in the unsaturated zone. Subsequently, two recently developed models were innovatively applied to the context of microbial contamination. The Active Region Model was evaluated as an alternative to the traditional, uniform flow model (Richard’s equation) to describe bacterial transport in a wastewater treatment facility. It resulted in removal rates that were two orders of magnitude smaller than the traditional approach, more consistently with observations. The study moreover assessed the relevance of a spatial probit model to estimate the probability of groundwater source contamination with thermotolerant coliforms in a case study in Juba, South Sudan. A conventional probit regression model resulted in spatially auto-correlated residuals, pointing to that the spatial model was more accurate. The results of this approach indicated that the local topography and the near presence of areas with informal settlements (Tukul zones) were associated with contamination. Statistical analyses moreover suggested that the depth of cumulative, long-term antecedent rainfall and on-site hygiene were significant risk factors. The findings indicated that the contributing groundwater was contaminated in Juba, and that contamination could be both local and regional in extent. They are relevant for environments with similar climatic, hydrogeological and socioeconomic characteristics, which are common in Sub-Saharan Africa. The results indicated that it is important to consider spatial interactions in this subject area. There is a need for studies that assess the distance within which such interactions can occur, using both mechanistic and statistical methods. Lastly, the results in this study consistently emphasized the importance of flow patterns for E. coli transport. It is thus recommended that future studies evaluate how models of preferential flow and transport can incorporate microbial fate. The multidisciplinary nature of the subject calls for a systems approach and collaboration between disciplines.
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| 7. |
- Engström, Emma, et al.
(författare)
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Prevalence of microbiological contaminants in groundwater sources and risk factor assessment in Juba, South Sudan
- 2015
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Ingår i: Science of the Total Environment. - : Elsevier B.V.. - 0048-9697 .- 1879-1026. ; 515-516, s. 181-187
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Tidskriftsartikel (refereegranskat)abstract
- In low-income regions, drinking water is often derived from groundwater sources, which might spread diarrheal disease if they are microbiologically polluted. This study aimed to investigate the occurrence of fecal contamination in 147 improved groundwater sources in Juba, South Sudan and to assess potential contributing risk factors, based on bivariate statistical analysis. Thermotolerant coliforms (TTCs) were detected in 66% of the investigated sources, including 95 boreholes, breaching the health-based recommendations for drinking water. A significant association (p<. 0.05) was determined between the presence of TTCs and the depth of cumulative, long-term prior precipitation (both within the previous five days and within the past month). No such link was found to short-term rainfall, the presence of latrines or damages in the borehole apron. However, the risk factor analysis further suggested, to a lesser degree, that the local topography and on-site hygiene were additionally significant. In summary, the analysis indicated that an important contamination mechanism was fecal pollution of the contributing groundwater, which was unlikely due to the presence of latrines; instead, infiltration from contaminated surface water was more probable. The reduction in fecal sources in the environment in Juba is thus recommended, for example, through constructing latrines or designating protection areas near water sources. The study results contribute to the understanding of microbiological contamination of groundwater sources in areas with low incomes and high population densities, tropical climates and weathered basement complex environments, which are common in urban sub-Saharan Africa.
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| 8. |
- Engström, Emma, et al.
(författare)
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Water Transport, Retention, and Survival of Escherichia coli in Unsaturated Porous Media : A Comprehensive Review of Processes, Models, and Factors
- 2015
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Ingår i: Critical reviews in environmental science and technology. - : Informa UK Limited. - 1064-3389 .- 1547-6537. ; 45:1
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Forskningsöversikt (refereegranskat)abstract
- The vadose zone can function as both a filter and a passage for bacteria. This review evaluates when and why either effect will apply based on available literature. It summarizes theories and experimental research that address the related, underlying bacterial attenuation processes, the applied macro-scale modeling approaches, and the influencing factors - including the cell, soil, solution and system characteristics. Results point to that the relative importance of each removal mechanism depends on the moisture content and the solution ionic strength. The limitations of available modeling approaches are discussed. It remains unclear in which contexts these are reliable for predictions. The temporal first-order kinetic Escherichia coli (E. coli) removal coefficient ranges three orders of magnitude, from 10(-4) to 10(-1)/min. Results suggest that this rate depends on the pore-water velocity. Spatial filtration of E. coli increases with slower flow and higher collector surface heterogeneity. It could be insignificant in the case of heavy and sudden infiltration and subsequent transport in preferential flow paths, induced, for example, by plant roots or cracks in clayey soils. Future research thus needs to address transport as an effect of extreme weather events such as droughts and subsequent floods.
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| 9. |
- Ingri, Johan, et al.
(författare)
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Iron isotope pathways in the boreal landscape : Role of the riparian zone
- 2018
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Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier. - 0016-7037 .- 1872-9533 .- 0046-564X. ; 239, s. 49-60
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Tidskriftsartikel (refereegranskat)abstract
- Stable Fe isotope compositions have been measured in water samples of the subarctic Kalix River, a first-order stream, and soil water samples from a riparian soil profile adjacent to the first-order stream (Northern Sweden). In the first-order stream, dominated by forest, both the particulate (>0.22 µm) and dissolved (<0.22 µm) phase showed negative δ56Fe values (relative to IRMM-014) during base flow and meltwater discharge in May (−0.97 to −0.09‰). The Fe isotope composition in the water from the riparian soil profile varied between −0.20 and +0.91‰ with sharp gradients near the groundwater table. A linear correlation between the δ56Fe values and the TOC/Febulk ratio was measured during snowmelt in the unfiltered river waters (δ56Fe from −0.02 to +0.54‰), suggesting mixing of two Fe components. Two groups of Fe aggregates, with different Fe isotope compositions, are formed in the boreal landscape. We propose that carbon-rich aggregates, Fe(II)(III)-OC, have negative δ56Fe values and Fe-oxyhydroxides have positive δ56Fe values. A mixture of these two components can explain temporal variations of the Fe isotope composition in the Kalix River. This study suggests that stable Fe isotopes can be used as a tool to track and characterize suspended Fe-organic carbon aggregates during transport from the soil, via first-order streams and rivers, to coastal sediment. Furthermore, the differences in Fe isotope values in the Kalix River and the first-order stream during base flow conditions suggest that the primary Fe sources for river water change throughout the year. This model is combining the Fe isotope composition of first-order streams and rivers to weathering and transport processes in the riparian soil.
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| 10. |
- Kullgren, Anders, 1963, et al.
(författare)
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The potential of vehicle and road infrastructure interventions in fatal bicyclist accidents on Swedish roads—What can in-depth studies tell us?
- 2019
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Ingår i: Traffic Injury Prevention. - : Informa UK Limited. - 1538-9588 .- 1538-957X. ; 20:sup1, s. S7-S12
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The objective of this article is to describe the characteristics of fatal crashes with bicyclists on Swedish roads in rural and urban areas and to investigate the potential of bicycle helmets and different vehicle and road infrastructure interventions to prevent them. The study has a comprehensive approach to provide road authorities and vehicle manufacturers with recommendations for future priorities. Methods: The Swedish Transport Administration’s (STA) in-depth database of fatal crashes was used for case-by-case analysis of fatal cycling accidents (2006–2016) on rural (n = 82) and urban (n = 102) roads. The database consists of information from the police, medical journals, autopsy reports, accident analyses performed by STA, and witness statements. The potential of helmet use and various vehicle and road infrastructure safety interventions was determined retrospectively for each case by analyzing the chain of events leading to the fatality. The potential of vehicle safety countermeasures was analyzed based on prognoses on their implementation rates in the Swedish vehicle fleet. Results: The most common accident scenario on rural roads was that the bicyclist was struck while cycling along the side of the road. On urban roads, the majority of accidents occurred in intersections. Most accidents involved a passenger car, but heavy trucks were also common, especially in urban areas. Most accidents occurred in daylight conditions (73%). Almost half (46%) of nonhelmeted bicyclists would have survived with a helmet. It was assessed that nearly 60% of the fatal accidents could be addressed by advanced vehicle safety technologies, especially autonomous emergency braking with the ability to detect bicyclists. With regard to interventions in the road infrastructure, separated paths for bicyclists and bicycle crossings with speed calming measures were found to have the greatest safety potential. Results indicated that 91% of fatally injured bicyclists could potentially be saved with known techniques. However, it will take a long time for such technologies to be widespread. Conclusions: The majority of fatally injured bicyclists studied could potentially be saved with known techniques. A speedy implementation of important vehicle safety systems is recommended. A fast introduction of effective interventions in the road infrastructure is also necessary, preferably with a plan for prioritization.
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