| 1. |
- Barregård, Lars, 1948, et al.
(författare)
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Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
- 2013
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
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| 2. |
- Jensen, M. S., et al.
(författare)
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Phospholipid flipping involves a central cavity in P4 ATPases
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- P4 ATPase flippases translocate phospholipids across biomembranes, thus contributing to the establishment of transmembrane lipid asymmetry, a feature important for multiple cellular processes. The mechanism by which such phospholipid flipping occurs remains elusive as P4 ATPases transport a giant substrate very different from that of other P-type ATPases such as Na+/K+-and Ca2+-ATPases. Based on available crystal structures of cation-transporting P-type ATPases, we generated a structural model of the broad-specificity flippase ALA10. In this model, a cavity delimited by transmembrane segments TM3, TM4, and TM5 is present in the transmembrane domain at a similar position as the cation-binding region in related P-type ATPases. Docking of a phosphatidylcholine headgroup in silico showed that the cavity can accommodate a phospholipid headgroup, likely leaving the fatty acid tails in contact with the hydrophobic portion of the lipid bilayer. Mutagenesis data support this interpretation and suggests that two residues in TM4 (Y374 and F375) are important for coordination of the phospholipid headgroup. Our results point to a general mechanism of lipid translocation by P4 ATPases, which closely resembles that of cation-transporting pumps, through coordination of the hydrophilic portion of the substrate in a central membrane cavity.
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| 3. |
- Petkevicius, K., et al.
(författare)
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TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The regulation of cellular phosphatidylethanolamine (PE) acyl chain composition is poorly understood. Here, the authors show that TLCD1 and TLCD2 proteins mediate the formation of monounsaturated fatty acid-containing PE species and promote the progression of non-alcoholic steatohepatitis. The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition. We generated Tlcd1/2 double-knockout (DKO) mice and found that they have reduced levels of hepatic monounsaturated fatty acid (MUFA)-containing PE species. Mechanistically, TLCD1/2 proteins act cell intrinsically to promote the incorporation of MUFAs into PEs. Furthermore, TLCD1/2 interact with the mitochondria in an evolutionarily conserved manner and regulate mitochondrial PE composition. Lastly, we demonstrate the biological relevance of our findings in dietary models of metabolic disease, where Tlcd1/2 DKO mice display attenuated development of non-alcoholic steatohepatitis compared to controls. Overall, we identify TLCD1/2 proteins as key regulators of cellular PE composition, with our findings having broad implications in understanding and treating disease.
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| 4. |
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| 5. |
- Ohrlander, M., et al.
(författare)
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The effect of electron beam irradiation on PCL and PDXO-X monitored by luminescence and electron spin resonance measurements
- 2000
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Ingår i: Polymer. - 0032-3861 .- 1873-2291. ; 41:4, s. 1277-1286
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Tidskriftsartikel (refereegranskat)abstract
- The effect of electron beam irradiation in air or argon was studied on two hydrolysable aliphatic polyesters, poly(e-caprolactone) (PCL) and chemically cross-linked poly(1,5-dioxepan-2-one) (PDXO-X). A secondary alkylether radical and a tertiary alkyl radical were identified by ESR in PCL and PDXO-X after irradiation in both air and argon. For the samples irradiated in air, peroxy radicals were detected in PCL but not in PDXO-X. For irradiated PCL, the intensities in the luminescence measurements seemed to be dose-dependent. Large amounts of oxidation products were found present in the PDXO-X irradiated in air and the luminescence intensities seemed to be dose-dependent.The effect of electron beam irradiation in air or argon was studied on two hydrolysable aliphatic polyesters, poly(e-caprolactone) (PCL) and chemically cross-linked poly(1,5-dioxepan-2-one) (PDXO-X). A secondary alkylether radical and tertiary alkyl radical were identified by ESR in PCL and PDXO-X after irradiation in both air and argon. For the samples irradiated in air, peroxy radicals were detected in PCL but not in PDXO-X. For irradiated PCL, the intensities in the luminescence measurements seemed to be dose-dependent. Large amounts of oxidation products were found present in the PDXO-X irradiated in air and the luminescence intensities seemed to be dose-dependent.
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| 6. |
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| 7. |
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| 8. |
- Bill-Axelson, Anna, et al.
(författare)
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Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer
- 2014
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Ingår i: New England Journal of Medicine. - Waltham : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 370:10, s. 932-942
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRadical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain. MethodsBetween 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy. ResultsDuring 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04). ConclusionsExtended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.) The randomized Swedish trial of prostatectomy versus watchful waiting in disease detected mainly clinically (not by PSA screening) continues to show a benefit for early prostatectomy. The number of men younger than 65 needed to treat to prevent one death is now four. The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer diagnosed before the era of prostate-specific antigen (PSA) testing, showed a survival benefit of radical prostatectomy as compared with observation at 15 years of follow-up.(1) By contrast, the Prostate Cancer Intervention versus Observation Trial (PIVOT), initiated in the early era of PSA testing, showed that radical prostatectomy did not significantly reduce prostate cancer-specific or overall mortality after 12 years.(2) PSA screening profoundly changes the clinical domain of study. Among other considerations, the substantial additional lead time ...
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| 9. |
- Bill-Axelson, Anna, et al.
(författare)
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Radical prostatectomy versus watchful waiting in early prostate cancer.
- 2011
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Ingår i: The New England journal of medicine. - : Massachussetts Medical Society. - 1533-4406 .- 0028-4793. ; 364:18, s. 1708-17
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Forskningsöversikt (refereegranskat)abstract
- In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results.
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| 10. |
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| 11. |
- Borestrom, C., et al.
(författare)
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A CRISP(e)R view on kidney organoids allows generation of an induced pluripotent stem cell-derived kidney model for drug discovery
- 2018
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Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 94:6, s. 1099-1110
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Tidskriftsartikel (refereegranskat)abstract
- Development of physiologically relevant cellular models with strong translatability to human pathophysiology is critical for identification and validation of novel therapeutic targets. Herein we describe a detailed protocol for generation of an advanced 3-dimensional kidney cellular model using induced pluripotent stem cells, where differentiation and maturation of kidney progenitors and podocytes can be monitored in live cells due to CRISPR/Cas9-mediated fluorescent tagging of kidney lineage markers (SIX2 and NPHS1). Utilizing these cell lines, we have refined the previously published procedures to generate a new, higher throughput protocol suitable for drug discovery. Using paraffin-embedded sectioning and whole-mount immunostaining, we demonstrated that organoids grown in suspension culture express key markers of kidney biology (WT1, ECAD, LTL, nephrin) and vasculature (CD31) within renal cortical structures with microvilli, tight junctions and podocyte foot processes visualized by electron microscopy. Additionally, the organoids resemble the adult kidney transcriptomics profile, thereby strengthening the translatability of our in vitro model. Thus, development of human nephron-like structures in vitro fills a major gap in our ability to assess the effect of potential treatment on key kidney structures, opening up a wide range of possibilities to improve clinical translation.
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| 12. |
- Borrega, M., et al.
(författare)
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Utilizing and Valorizing Oat and Barley Straw as an Alternative Source of Lignocellulosic Fibers
- 2022
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Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 15:21
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Tidskriftsartikel (refereegranskat)abstract
- The transition to sustainable, biodegradable, and recyclable materials requires new sources of cellulose fibers that are already used in large volumes by forest industries. Oat and barley straws provide interesting alternatives to wood fibers in lightweight material applications because of their similar chemical composition. Here we investigate processing and material forming concepts, which would enable strong fiber network structures for various applications. The idea is to apply mild pretreatment processing that could be distributed locally so that the logistics of the raw material collection could be made efficient. The actual material production would then combine foam-forming and hot-pressing operations that allow using all fractions of fiber materials with minimal waste. We aimed to study the technical features of this type of processing on a laboratory scale. The homogeneity of the sheet samples was very much affected by whether the raw material was mechanically refined or not. Straw fibers did not form a bond spontaneously with one another after drying the sheets, but their effective bonding required a subsequent hot pressing operation. The mechanical properties of the formed materials were at a similar level as those of the conventional wood-fiber webs. In addition to the technical aspects of materials, we also discuss the business opportunities and system-level requirements of using straw as an alternative source of lignocellulosic fibers.
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| 13. |
- Chapman, Elizabeth A., et al.
(författare)
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Perennials as Future Grain Crops : Opportunities and Challenges
- 2022
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Ingår i: Frontiers in Plant Science. - : Frontiers Media SA. - 1664-462X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Perennial grain crops could make a valuable addition to sustainable agriculture, potentially even as an alternative to their annual counterparts. The ability of perennials to grow year after year significantly reduces the number of agricultural inputs required, in terms of both planting and weed control, while reduced tillage improves soil health and on-farm biodiversity. Presently, perennial grain crops are not grown at large scale, mainly due to their early stages of domestication and current low yields. Narrowing the yield gap between perennial and annual grain crops will depend on characterizing differences in their life cycles, resource allocation, and reproductive strategies and understanding the trade-offs between annualism, perennialism, and yield. The genetic and biochemical pathways controlling plant growth, physiology, and senescence should be analyzed in perennial crop plants. This information could then be used to facilitate tailored genetic improvement of selected perennial grain crops to improve agronomic traits and enhance yield, while maintaining the benefits associated with perennialism.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Ketzel, M, et al.
(författare)
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Particle and trace gas emission factors under urban driving conditions in Copenhagen based on street and roof-level observations
- 2003
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Ingår i: Atmospheric Environment. - 1352-2310. ; 37:20, s. 2735-2749
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Tidskriftsartikel (refereegranskat)abstract
- Simultaneous measurements of particle size distribution (size/range 10-700 nm) inside an urban street canyon and a nearby urban background location in Copenhagen in May-November 2001 were used to separate the traffic source contribution in the street canyon from the background levels. The background concentrations are highly variable due to changing contributions from long-range transport and local sources showing a diurnal pattern with a shift to smaller particle sizes during midday hours. The average ratio background/street concentration is 0.26 for NOx and 0.35, 0.42, 0.60, 0.64, respectively, for CO, total particle number (ToN), surface and volume. The particle size distribution of the traffic source shows during daytime and evening hours (6-24) a maximum at particle sizes of 20-30 nm independent of the changing heavy-duty vehicle share during the same time interval. The particle number concentration highly correlated (R > 0.83) with NOx through a wide range of particle sizes. The method of inverse modelling was applied to estimate average fleet emission factors typical of urban conditions in Denmark. Emission factors per average vehicle were estimated as (2.8 +/- 0.5) x 10(14) particles/km, (1.3 +/- 0.2) g NOx/(veh km) and (11 +/- 2) g CO/(veh km). We observe two types of 'nanoparticle events' (a) in background, probably due to photochemistry and (b) in the night hours when traffic is dominated by diesel taxis. During night hours (0-5), the maximum in the emitted particle size distribution, is shifted to smaller sizes of about 15-18 nm. This shift to smaller particle sizes is related to an increase in the average NOx and ToN emission per vehicle by a factor of 2-3 and a reduced CO emission also by a factor of 2-3. (C) 2003 Elsevier Science Ltd. All rights reserved.
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| 20. |
- Ketzel, M, et al.
(författare)
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Particle size distribution and particle mass measurements at urban, near-city and rural level in the Copenhagen area and Southern Sweden
- 2004
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Ingår i: Atmospheric Chemistry and Physics. - 1680-7324. ; 4, s. 281-292
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Tidskriftsartikel (refereegranskat)abstract
- Particle size distribution (size-range 3-900 nm) and PM10 was measured simultaneously at an urban background station in Copenhagen, a near-city background and a rural location during a period in September-November 2002. The study investigates the contribution from urban versus regional sources of particle number and mass concentration. The total particle number (ToN) and NOx are well correlated at the urban and near-city level and show a distinct diurnal variation, indicating the common traffic source. The average ToN at the three stations differs by a factor of 3. The observed concentrations are 2500# cm(-3), 4500# cm(-3) and 7700# cm(-3) at rural, near-city and urban level, respectively. PM10 and total particle volume (ToV) are well correlated between the three different stations and show similar concentration levels, in average within 30% relative difference, indicating a common source from long-range transport that dominates the concentrations at all locations. Measures to reduce the local urban emissions of NOx and ToN are likely to affect both the street level and urban background concentrations, while for PM10 and ToV only measurable effects at the street level are probable. Taking into account the supposed stronger health effects of ultrafine particles reduction measures should address particle number emissions. The traffic source contributes strongest in the 10-200 nm particle size range. The maximum of the size distribution shifts from about 20-30 nm at kerbside to 50-60 nm at rural level. Particle formation events were observed in the 3-20 nm size range at rural location in the afternoon hours, mainly under conditions with low concentrations of preexisting aerosol particles. The maximum in the size distribution of the "traffic contribution" seems to be shifted to about 28 nm in the urban location compared to 22 nm at kerbside. Assuming NOx as an inert tracer on urban scale allows to estimate that ToN at urban level is reduced by 15-30% compared to kerbside. Particle removal processes, e. g. deposition and coagulation, which are most efficient for smallest particle sizes (<20 nm) and condensational growth are likely mechanisms for the loss of particle number and the shift in particle size.
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| 21. |
- Lucchini, Roberto G., et al.
(författare)
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Inverse association of intellectual function with very low blood lead but not with manganese exposure in Italian adolescents
- 2012
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Ingår i: Environmental Research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 118, s. 65-71
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pediatric lead (Pb) exposure impacts cognitive function and behavior and co-exposure to manganese (Mn) may enhance neurotoxicity. Objectives: To assess cognitive and behavioral function in adolescents with environmental exposure to Pb and Mn. Methods: In this cross sectional study, cognitive function and behavior were examined in healthy adolescents with environmental exposure to metals. The Wechsler Intelligence Scale for Children (WISC) and the Conners-Wells' Adolescent Self-Report Scale Long Form (CASS:L) were used to assess cognitive and behavioral function, respectively. ALAD polymorphisms rs1800435 and rs1139488 were measured as potential modifiers. Results: We examined 299 adolescents (49.2% females) aged 11-14 years. Blood lead (BPb) averaged 1.71 mu g/dL (median 1.5, range 0.44-10.2), mean Blood Manganese (BMn) was 11.1 mu g/dL (median 10.9, range 4.00-24.1). Average total IQ was 106.3 (verbal IQ= 102, performance IQ= 109.3). According to a multiple regression model considering the effect of other covariates, a reduction of about 2.4 IQ points resulted from a two-fold increase of BPb. The Benchmark Level of BPb associated with a loss of 1 IQ-point (BML01) was 0.19 mu g/dL, with a lower 95% confidence limit (BMLL01) of 0.11 mu g/dL. A very weak correlation resulted between BPb and the ADHD-like behavior (Kendall's tau rank correlation=0.074, p=0.07). No influence of ALAD genotype was observed on any outcome. Manganese was not associated with cognitive and behavioral outcomes, nor was there any interaction with lead. Conclusions: These findings demonstrate that very low level of lead exposure has a significant negative impact on cognitive function in adolescent children. Being an essential micro-nutrient, manganese may not cause cognitive effects at these low exposure levels. (c) 2012 Elsevier Inc. All rights reserved.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Palmgren, Helena, 1955-, et al.
(författare)
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Salmonella in sub-Antarctica : low heterogeneity in salmonella serotypes in South Georgian seals and birds
- 2000
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Ingår i: Epidemiology and Infection. - : Cambridge University Press. - 0950-2688 .- 1469-4409. ; 125:2, s. 257-262
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Tidskriftsartikel (refereegranskat)abstract
- The number of human visitors to Antarctica is increasing rapidly, and with it a risk of introducing infectious organisms to native animals. To study the occurrence of salmonella serotypes in sub- Antarctic wildlife, faecal samples were collected from gentoo penguins, macaroni penguins, gray-headed albatrosses, black-browed albatrosses and Antarctic fur seals on Bird Island in the South Georgian archipelago during the austral summer of 1996 and 1998. In 1996, S. havana, S. typhimurium and S. enteritidis were isolated from 7% of gentoo penguins and 4% of fur seals. In 1998, however, 22% of fur seals were found to be infected with S. havana, S. enteritidis and S. newport. All isolates, except one, showed identical pulsed-field gel electrophoresis-patterns within each serotype, irrespective of sampling year and animal reservoir. No significant antibiotic resistance was found. The very low heterogeneity in the salmonella isolates found could either indicate a high genetic adaptation of the bacteria to the environment or a recent introduction of salmonella into the area.
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| 27. |
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| 28. |
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| 29. |
- Ruiz, Mario, 1984, et al.
(författare)
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Extensive transcription mis-regulation and membrane defects in AdipoR2-deficient cells challenged with saturated fatty acids
- 2021
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Ingår i: Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981. ; 1866:4
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Tidskriftsartikel (refereegranskat)abstract
- How cells maintain vital membrane lipid homeostasis while obtaining most of their constituent fatty acids from a varied diet remains largely unknown. Here, we used transcriptomics, lipidomics, growth and respiration assays, and membrane property analyses in human HEK293 cells or human umbilical vein endothelial cells (HUVEC) to show that the function of AdipoR2 is to respond to membrane rigidification by regulating many lipid metabolism genes. We also show that AdipoR2-dependent membrane homeostasis is critical for growth and respiration in cells challenged with saturated fatty acids. Additionally, we found that AdipoR2 deficiency causes transcriptome and cell physiological defects similar to those observed in SREBP-deficient cells upon SFA challenge. Finally, we compared several genes considered important for lipid homeostasis, namely AdipoR2, SCD, FADS2, PEMT and ACSL4, and found that AdipoR2 and SCD are the most important among these to prevent membrane rigidification and excess saturation when human cells are challenged with exogenous SFAs. We conclude that AdipoR2-dependent membrane homeostasis is one of the primary mechanisms that protects against exogenous SFAs.
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| 30. |
- Sellberg, M, et al.
(författare)
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-A cross-sectional study of clinical learning environments across four undergraduate programs using the undergraduate clinical education environment measure
- 2021
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Ingår i: BMC medical education. - : Springer Science and Business Media LLC. - 1472-6920. ; 21:1, s. 258-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe clinical learning environment (CLE) influences students’ achievement of learning outcomes and the development of their professional behaviors. However, CLEs are not always optimal for learning because of clinical productivity expectations and a lack of support from supervisors. The purpose of this study was to describe and compare students’ perceptions of their CLEs across four undergraduate programs.MethodsThis study is cross-sectional. In total, 735 students who were registered in the medical, nursing, physiotherapy, and speech-language pathology (SLP) programs were invited to participate. Data were collected using an online survey, which included demographics and the Undergraduate Clinical Education Environment Measure (UCEEM). The UCEEM consists of 26 items congregated into two overarching dimensions—experiential learning and social participation—with four subscales: opportunities to learn in and through work and quality of supervision, preparedness for student entry, workplace interaction patterns and student inclusion, and equal treatment.ResultsIn total 280 students (median age 28; range: 20–52; 72% females) returned the questionnaire. The mean total UCEEM score was 98.3 (SD 18.4; range: 91–130), with physiotherapy students giving the highest scores and medical students the lowest. The mean scores for the dimensions experiential learning and social participation for all the students were 62.8 (SD 13.6; range 59–85) and 35.5 (SD 6.2; range 13–45), respectively. Medical students rated the lowest for all subscales. The items receiving the highest ratings concerned equal treatment, whereas those receiving the lowest ratings concerned supervisors’ familiarity with the learning objectives. There were few statistically significant differences between the semesters within each program.ConclusionsThe students generally hold positive perceptions toward their CLEs. However, the students from the medical and nursing programs rated their learning environment lower than did the students from the physiotherapy and SLP programs. Importantly, in several aspects, the medical students provided significantly lower ratings for their CLE compared with the students from the other programs. The medical students’ low ratings for their supervisors’ familiarity with the learning objectives underscore the need to ensure that the prerequisites for optimal supervision are met.
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| 31. |
- Spjuth, Ola, 1977-, et al.
(författare)
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Harmonising and linking biomedical and clinical data across disparate data archives to enable integrative cross-biobank research
- 2016
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 24:4, s. 521-528
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Tidskriftsartikel (refereegranskat)abstract
- A wealth of biospecimen samples are stored in modern globally distributed biobanks. Biomedical researchers worldwide need to be able to combine the available resources to improve the power of large-scale studies. A prerequisite for this effort is to be able to search and access phenotypic, clinical and other information about samples that are currently stored at biobanks in an integrated manner. However, privacy issues together with heterogeneous information systems and the lack of agreed-upon vocabularies have made specimen searching across multiple biobanks extremely challenging. We describe three case studies where we have linked samples and sample descriptions in order to facilitate global searching of available samples for research. The use cases include the ENGAGE (European Network for Genetic and Genomic Epidemiology) consortium comprising at least 39 cohorts, the SUMMIT (surrogate markers for micro- and macro-vascular hard endpoints for innovative diabetes tools) consortium and a pilot for data integration between a Swedish clinical health registry and a biobank. We used the Sample avAILability (SAIL) method for data linking: first, created harmonised variables and then annotated and made searchable information on the number of specimens available in individual biobanks for various phenotypic categories. By operating on this categorised availability data we sidestep many obstacles related to privacy that arise when handling real values and show that harmonised and annotated records about data availability across disparate biomedical archives provide a key methodological advance in pre-analysis exchange of information between biobanks, that is, during the project planning phase.
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| 32. |
- Wahlberg, Karin E, et al.
(författare)
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Common polymorphisms in the solute carrier SLC30A10 are associated with blood manganese and neurological function.
- 2016
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-0929 .- 1096-6080. ; 149:2, s. 473-483
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Tidskriftsartikel (refereegranskat)abstract
- Manganese (Mn) is an essential nutrient in humans, but excessive exposure to Mn may cause neurotoxicity. Despite homeostatic regulation, Mn concentrations in blood vary considerably among individuals. We evaluated if common single-nucleotide polymorphisms (SNPs) in SLC30A10, which likely encodes a Mn transporter, influence blood Mn concentrations and neurological function. We measured blood Mn concentrations by ICP-MS or atomic absorption spectroscopy and genotyped two SLC30A10 non-coding SNPs (rs2275707 and rs12064812) by TaqMan PCR in cohorts from Bangladesh (N=406), the Argentinean Andes (N=198), and Italy (N=238). We also measured SLC30A10 expression in whole blood by TaqMan PCR in a sub-group (N=101) from the Andean cohort, and neurological parameters (sway velocity and finger-tapping speed) in the Italian cohort.The rs2275707 variant allele was associated with increased Mn concentrations in the Andes (8%, p=0.027) and Italy (10.6%, p=0.012), but not as clear in Bangladesh (3.4%, p=0.21; linear regression analysis adjusted for age, gender, and plasma ferritin). This allele was also associated with increased sway velocity (15%, p=0.033; adjusted for age and sex) and reduced SLC30A10 expression (-24.6%, p=0.029). By contrast, the rs12064812 variant homozygous genotype was associated with reduced Mn concentrations, particularly in the Italian cohort (-18.4%, p=0.04), and increased finger-tapping speed (8.7%, p=0.025).We show that common SNPs in SLC30A10 are associated with blood Mn concentrations in three unrelated cohorts and that their influence may be mediated by altered SLC30A10 expression. Moreover, the SNPs appeared to influence neurological functions independent of blood Mn concentrations, suggesting that SLC30A10 could regulate brain Mn levels.
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