| 1. |
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| 2. |
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| 3. |
- Thoma, B, et al.
(författare)
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An international, interprofessional investigation of the self-reported podcast listening habits of emergency clinicians: A METRIQ Study
- 2020
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Ingår i: CJEM. - : Springer Science and Business Media LLC. - 1481-8043 .- 1481-8035. ; 22:1, s. 112-117
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesPodcasts are increasingly being used for medical education. A deeper understanding of usage patterns would inform both producers and researchers of medical podcasts. We aimed to determine how and why podcasts are used by emergency medicine and critical care clinicians.MethodsAn international interprofessional sample (medical students, residents, physicians, nurses, physician assistants, and paramedics) was recruited through direct contact and a multimodal social media (Twitter and Facebook) campaign. Each participant completed a survey outlining how and why they utilize medical podcasts. Recruitment materials included an infographic and study website.Results390 participants from 33 countries and 4 professions (medicine, nursing, paramedicine, physician assistant) completed the survey. Participants most frequently listened to medical podcasts to review new literature (75.8%), learn core material (75.1%), and refresh memory (71.8%). The majority (62.6%) were aware of the ability to listen at increased speeds, but most (76.9%) listened at 1.0 x (normal) speed. All but 25 (6.4%) participants concurrently performed other tasks while listening. Driving (72.3%), exercising (39.7%), and completing chores (39.2%) were the most common. A minority of participants used active learning techniques such as pausing, rewinding, and replaying segments of the podcast. Very few listened to podcasts multiple times.ConclusionsAn international cohort of emergency clinicians use medical podcasts predominantly for learning. Their listening habits (rarely employing active learning strategies and frequently performing concurrent tasks) may not support this goal. Further exploration of the impact of these activities on learning from podcasts is warranted.
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| 4. |
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| 6. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 7. |
- Kaput, J, et al.
(författare)
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The case for strategic international alliances to harness nutritional genomics for public and personal health
- 2005
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Ingår i: The British journal of nutrition. - : Cambridge University Press (CUP). - 0007-1145 .- 1475-2662. ; 94:5, s. 623-632
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Tidskriftsartikel (refereegranskat)abstract
- Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene–nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient–genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.
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| 8. |
- Berndt, Sonja I., et al.
(författare)
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Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P = 2.55 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
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| 9. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:8, s. 868-U202
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
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| 10. |
- Berndt, Sonja, I, et al.
(författare)
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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
- 2022
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Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
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Tidskriftsartikel (refereegranskat)abstract
- Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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| 11. |
- Correa, R. E., et al.
(författare)
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Submarine groundwater discharge and associated nutrient and carbon inputs into Sydney Harbour (Australia)
- 2020
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Ingår i: Journal of Hydrology. - : Elsevier BV. - 0022-1694. ; 580
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Tidskriftsartikel (refereegranskat)abstract
- The effects of urbanization and scales on submarine groundwater discharge (SGD) remain poorly understood. Here, we used radium isotopes to quantify SGD-derived fluxes of nitrogen, phosphorus and dissolved organic carbon (DOC) into Sydney Harbour estuary, Australia. Sydney is the most populated city of Oceania, with several localised cases of historical groundwater pollution. We sampled top and bottom waters at the harbour scale (~20 km) and also at four small scale embayments (~2 km). A decreasing gradient in radium isotope concentrations from upstream to downstream was observed. Mass balances constructed with 224Ra, 223Ra, and 226Ra revealed that total SGD ranged from 42 to 121 × 104 m3 d−1 depending on assumptions and isotope. These fluxes were related mostly to saline SGD (recirculated seawater), and are equivalent to >60 times the mean annual freshwater river discharge into Sydney Harbour (0.68 × 104 m3 d−1). The estimated SGD rates (2.2 ± 1.5 cm d−1) were comparable to the global average radium-derived-SGD in other urban estuaries (~3.1 cm d−1). No obvious relationships were observed between SGD and scale in Sydney Harbour. However, higher SGD rates estimated for embayments closer to the ocean indicate that a combination of waves, tides and urbanization control SGD. SGD derived fluxes exceeded maximum riverine nutrient fluxes by a factor of 2 for DOC, 6 for PO4 3−, 40 for NH4 + and 1.3 for NOX. Previous work has suggested that nutrients enter Sydney Harbour primarily through rivers or stormwater following episodic rain events. Our results imply that diffuse saline SGD can also be an important but overlooked source of nutrients, potentially sustaining primary productivity in times of no river flow. © 2019 Elsevier B.V.
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| 12. |
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| 13. |
- Reading, M. J., et al.
(författare)
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Submarine groundwater discharge drives nitrous oxide source/sink dynamics in a metropolitan estuary
- 2021
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Ingår i: Limnology and Oceanography. - : Wiley. - 0024-3590 .- 1939-5590. ; 66:5, s. 1665-1686
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Tidskriftsartikel (refereegranskat)abstract
- Coastal waterways can be significant sources of the potent greenhouse gas nitrous oxide (N2O) due to nitrogen inputs and eutrophication. Here, we quantify groundwater derived N2O inputs and atmospheric emissions within a modified urban embayment (Sydney Harbour, Australia). Overall, we found low N2O saturation (91-171%) and air-water fluxes (-2.2 to 24.6 mu mol m(-2) d(-1)). Concentrations were highest in upstream brackish areas and a commercial/industrial subembayment. Dissolved inorganic nitrogen concentrations were low and inversely correlated to N2O throughout the harbor. N2O surface water dynamics were apparently driven by saline submarine groundwater discharge, as quantified by the radioisotope tracer radon-222. Groundwater discharge was highest within the embayments and mangrove-lined upper estuary. While groundwater was a net N2O source to surface waters, two upstream sub-embayments featured groundwater N2O concentrations lower than surface water, suggesting a sink driven by surface waters recirculating in intertidal sediments. Surface-water N2O was undersaturated within one upstream embayment, likely due to N2O consumption within sediments. Contrastingly, the downstream embayments featured higher groundwater N2O and accounted for 45% +/- 21% of the groundwater N2O flux. Sydney Harbour was a net source of N2O to the atmosphere (mean 0.6 +/- 0.3 mu mol m(-2) d(-1)) with larger N2O fluxes occurring from relatively small areas. N2O emissions (expressed in CO2 equilivents) were equivalent to 17% of CO2 emission estimates from previous studies. The low N2O emissions in Sydney Harbour contrast with other modified estuaries which often emit higher N2O fluxes due to larger nitrogen inputs.
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| 14. |
- Santoro, Aurelia, et al.
(författare)
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Combating inflammaging through a Mediterranean whole diet approach : The NU-AGE project's conceptual framework and design
- 2014
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Ingår i: Mechanisms of Ageing and Development. - Clare, Ireland : Elsevier BV. - 0047-6374 .- 1872-6216. ; 136-137, s. 3-13
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Tidskriftsartikel (refereegranskat)abstract
- The development of a chronic, low grade, inflammatory status named "inflammaging" is a major characteristic of ageing, which plays a critical role in the pathogenesis of age-related diseases. Inflammaging is both local and systemic, and a variety of organs and systems contribute inflammatory stimuli that accumulate lifelong. The NU-AGE rationale is that a one year Mediterranean whole diet (considered by UNESCO a heritage of humanity), newly designed to meet the nutritional needs of the elderly, will reduce inflammaging in fully characterized subjects aged 65-79 years of age, and will have systemic beneficial effects on health status (physical and cognitive). Before and after the dietary intervention a comprehensive set of analyses, including omics (transcriptomics, epigenetics, metabolomics and metagenomics) will be performed to identify the underpinning molecular mechanisms. NU-AGE will set up a comprehensive database as a tool for a systems biology approach to inflammaging and nutrition. NU-AGE is highly interdisciplinary, includes leading research centres in Europe on nutrition and ageing, and is complemented by EU multinational food industries and SMEs, interested in the production of functional and enriched/advanced traditional food tailored for the elderly market, and European Federations targeting policy makers and major stakeholders, from consumers to EU Food & Drink Industries.
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| 15. |
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| 16. |
- Reading, M. J., et al.
(författare)
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Land use drives nitrous oxide dynamics in estuaries on regional and global scales
- 2020
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Ingår i: Limnology and Oceanography. - : Wiley. - 0024-3590 .- 1939-5590. ; 65:8, s. 1903-20
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Tidskriftsartikel (refereegranskat)abstract
- Urban and agricultural development of coastal catchments is known to increase dissolved nitrogen inputs into estuaries; however, much less is known about how land use influences the production of the powerful greenhouse gas nitrous oxide (N2O). Here, we assess dissolved N2O dynamics in four nearby estuaries across a regional land use gradient and summarize the literature to put the observations into global perspective. During summer dry conditions, N2O saturation ranged from 131.4% +/- 45.0% in the most pristine system (28% modified) to 198.6% +/- 52.3% within the most modified urban system (91% modified). The N2O saturation in the wetter winter campaign was higher and more variable than the summer dry campaign (range 84.7-677.7%) likely due to direct transport of N2O into the estuaries from catchment runoff and/or produced through denitrification fueled by high nitrate inputs. During both seasons, N2O was lowest in areas adjacent to fringing mangroves and highest in upstream fresh/saltwater mixing areas. Coupling our results with previously published N2O data from 50 estuarine systems worldwide revealed that estuarine N2O increases concomitantly with catchment modification, dissolved inorganic nitrogen availability, and decreasing oxygen concentrations. Based on these results, a 1% increase in anthropogenic modification to global catchments (i.e., agricultural development and/or urbanization) may increase estuarine N2O saturation by 2.6% +/- 1.2%. These findings indicate that future estuarine N2O emissions are likely to increase as anthropogenic modification of coastal catchments intensifies.
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| 17. |
- Reading, M. J., et al.
(författare)
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Spatial Distribution of CO2, CH4, and N2O in the Great Barrier Reef Revealed Through High Resolution Sampling and Isotopic Analysis
- 2021
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 48:15
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Tidskriftsartikel (refereegranskat)abstract
- Methane (CH4) and nitrous oxide (N2O) dynamics in coastal coral reef areas are poorly understood. We measured dissolved carbon dioxide (CO2) and CH4 (with delta C-13-CO2 and delta C-13-CH4 isotope fractions) and N2O in the Great Barrier Reef (GBR) to determine spatial distributions and emissions. CO2 (379-589 mu atm) was oversaturated due to calcification and riverine sources, as indicated by depleted delta C-13-CO2 values. CH4 (1.5-13.5 nM) was also oversaturated from nearshore biogenic sources indicated by depleted delta C-13-CH4 and probable offshore aerobic production. N2O (5.5-6.6 nM) was generally undersaturated, with uptake highest near the coast. Daily CO2 emissions were 5826 +/- 1191 tonnes, with CO2 equivalent ((eq)) N2O uptake (191 +/- 44 tonnes) offsetting 3.3% of CO2 or 89% of CH4eq (214 +/- 45 tonnes) emissions based on 20-year global warming potentials. The GBR was a slight CO2 and CH4 source and N2O sink during our study. However, further work is required to constrain diurnal, seasonal, and spatial dynamics.
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| 18. |
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| 19. |
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| 20. |
- Sclafani, F., et al.
(författare)
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Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer : results of the EXPERT-C trial
- 2015
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 26:9, s. 1936-1941
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Tidskriftsartikel (refereegranskat)abstract
- Lethal-7 (let-7) is a tumour suppressor miRNA which acts by down-regulating several oncogenes including KRAS. A single-nucleotide polymorphism (rs61764370, T > G base substitution) in the let-7 complementary site 6 (LCS-6) of KRAS mRNA has been shown to predict prognosis in early-stage colorectal cancer (CRC) and benefit from anti-epidermal growth factor receptor monoclonal antibodies in metastatic CRC. We analysed rs61764370 in EXPERT-C, a randomised phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX plus or minus cetuximab in locally advanced rectal cancer. DNA was isolated from formalin-fixed paraffin-embedded tumour tissue and genotyped using a PCR-based commercially available assay. Kaplan-Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms. A total of 155/164 (94.5%) patients were successfully analysed, of whom 123 (79.4%) and 32 (20.6%) had the LCS-6 TT and LCS-6 TG genotype, respectively. Carriers of the G allele were found to have a statistically significantly higher rate of complete response (CR) after neoadjuvant therapy (28.1% versus 10.6%; P = 0.020) and a trend for better 5-year progression-free survival (PFS) [77.4% versus 64.5%: hazard ratio (HR) 0.56; P = 0.152] and overall survival (OS) rates (80.3% versus 71.9%: HR 0.59; P = 0.234). Both CR and survival outcomes were independent of the use of cetuximab. The negative prognostic effect associated with KRAS mutation appeared to be stronger in patients with the LCS-6 TT genotype (HR PFS 1.70, P = 0.078; HR OS 1.79, P = 0.082) compared with those with the LCS-6 TG genotype (HR PFS 1.33, P = 0.713; HR OS 1.01, P = 0.995). This analysis suggests that rs61764370 may be a biomarker of response to neoadjuvant treatment and an indicator of favourable outcome in locally advanced rectal cancer possibly by mitigating the poor prognosis of KRAS mutation. In this setting, however, this polymorphism does not appear to predict cetuximab benefit.
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| 21. |
- Tait, D. R., et al.
(författare)
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Submarine Groundwater Discharge Exceeds River Inputs as a Source of Nutrients to the Great Barrier Reef
- 2023
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Ingår i: Environmental Science & Technology. - 0013-936X. ; 57:41, s. 15627-15634
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Tidskriftsartikel (refereegranskat)abstract
- Rivers are often assumed to be the main source of nutrients triggering eutrophication in the Great Barrier Reef (GBR). However, existing nutrient budgets suggest a major missing source of nitrogen and phosphorus sustaining primary production. Here, we used radium isotopes to resolve submarine groundwater discharge (SGD)-derived, shelf-scale nutrient inputs to the GBR. The total SGD was similar to 10-15 times greater than average river inputs, with nearshore groundwater discharge accounting for similar to 30% of this. Total SGD accounted for >30% of all known dissolved inorganic N and >60% of inorganic P inputs and exceeded regional river inputs. However, SGD was only a small proportion of the nutrients necessary to sustain primary productivity, suggesting that internal recycling processes still dominate the nutrient budget. With millions of dollars spent managing surface water nutrient inputs to reef systems globally, we argue for a shift in the focus of management to safeguard reefs from the impacts of excess nutrients.
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| 22. |
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| 23. |
- Carli, F, et al.
(författare)
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Exposure to Endocrine Disruptors (Di(2-Ethylhexyl)phthalate (DEHP) and Bisphenol A (BPA)) in Women from Different Residing Areas in Italy: Data from the LIFE PERSUADED Project
- 2022
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 23:24
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Tidskriftsartikel (refereegranskat)abstract
- Phthalates and bisphenol A (BPA) are plasticizers used in many industrial products that can act as endocrine disruptors and lead to metabolic diseases. During the LIFE PERSUADED project, we measured the urinary concentrations of BPA and Di(2-ethylhexyl)phthalate (DEHP) metabolites in 900 Italian women representative of the Italian female adult population (living in the north, centre, and south of Italy in both rural and urban areas). The whole cohort was exposed to DEHP and BPA with measurable levels above limit of detection in more than 99% and 95% of the samples, respectively. The exposure patterns differed for the two chemicals in the three macro-areas with the highest urinary levels for DEHP in south compared to central and northern Italy and for BPA in northern compared to central and southern Italy. BPA levels were higher in women living in urban areas, whereas no difference between areas was observed for DEHP. The estimated daily intake of BPA was 0.11 μg/kg per day, about 36-fold below the current temporary tolerable daily intake of 4 μg/kg per day established by the EFSA in 2015. The analysis of cumulative exposure showed a positive correlation between DEHP and BPA. Further, the reduction of exposure to DEHP and BPA, through specific legislative measures, is necessary to limit the harmfulness of these substances.
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| 24. |
- Fairweather-Tait, S, et al.
(författare)
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The usefulness of in vitro models to predict the bioavailability of iron and zinc: A consensus statement from the HarvestPlus Expert Consultation
- 2005
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Ingår i: International Journal for Vitamin and Nutrition Research. - : Hogrefe Publishing Group. - 0300-9831 .- 1664-2821. ; 75:6, s. 371-374
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Tidskriftsartikel (refereegranskat)abstract
- A combination of dietary and host-related factors determines iron and zinc absorption, and several in vitro methods have been developed as preliminary screening tools for assessing bioavailability. An expert committee has reviewed evidence for their usefulness and reached a consensus. Dialyzability (with and without simulated digestion) gives some useful information but cannot predict the correct magnitude of response and may sometimes predict the wrong direction of response. Caco-2 cell systems (with and without simulated digestion) have been developed for iron availability, but the magnitude of different effects does not always agree with results obtained in human volunteers, and the data for zinc are too limited to draw conclusions about the validity of the method. Caco-2 methodologies vary significantly between laboratories and require experienced technicians and good quality cell culture facilities to obtain reproducible results. Algorithms can provide semi-quantitative information enabling diets to be classified as high, moderate, or low bioavailability. While in vitro methods can be used to generate ideas and develop hypotheses, they cannot be used alone for important decisions concerning; food fortification policy, selection of varieties for plant breeding programs, or for new product development in the food industry. Ultimately human studies are required for such determinations.
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| 25. |
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| 26. |
- Sclafani, F., et al.
(författare)
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PAN-EX : a pooled analysis of two trials of neoadjuvant chemotherapy followed by chemoradiotherapy in MRI-defined, locally advanced rectal cancer
- 2016
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:8, s. 1557-1565
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Tidskriftsartikel (refereegranskat)abstract
- This analysis confirms that administering neoadjuvant chemotherapy (NACT) before chemoradiotherapy (CRT) could be a potential option for high-risk, locally advanced rectal cancer. In this setting, MRI tumour regression grade is an independent prognostic factor and, when assessed after NACT, may predict the probability and magnitude of incremental benefit from sequential CRT.EXPERT and EXPERT-C were phase II clinical trials of neoadjuvant chemotherapy (NACT) followed by chemoradiotherapy (CRT) in high-risk, locally advanced rectal cancer (LARC). We pooled individual patient data from these trials. The primary objective was overall survival (OS) in the intention-to-treat (ITT) population. Prognostic factors were also analysed. A total of 269 patients were included. Of these, 91.1% completed NACT, 88.1% completed CRT and 240 (89.2%) underwent curative surgery (R0/R1). After a median follow-up of 71.9 months, 5-year progression-free survival (PFS) and OS were 66.4% and 73.3%, respectively. In the group of R0/R1 resection patients, 5-year relapse-free survival (RFS) and OS were 71.6% and 77.2%, respectively, with local recurrence occurring in 5.5% and distant metastases in 20.6% of cases. Significant prognostic factors after multivariate analyses included age, tumour grade and MRI extramural venous invasion (mrEMVI) at baseline, MRI tumour regression grade (mrTRG) after CRT, ypT stage after surgery and adherence to study treatment. mrTRG after NACT was associated with PFS (P = 0.002) and OS (P = 0.018) and appeared to stratify patients based on the incremental benefit from sequential CRT. Among the outcome measures considered, in the subgroup of R0/R1 resection patients, ypT and ypStage had the highest predictive accuracy for RFS (concordance index: 0.6238 and 0.6252, respectively) and OS (concordance index: 0.6094 and 0.6132, respectively). Administering NACT before CRT could be a potential strategy for high-risk LARC. In this setting, mrTRG after CRT is an independent prognostic factor, while mrTRG after NACT should be tested as a parameter for treatment selection in trials of NACT +/- CRT. ypT stage may be a valuable surrogate end point for future phase II trials investigating intensified neoadjuvant treatments in similar patient populations.
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| 27. |
- Černok, Ana, et al.
(författare)
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Lunar samples record an impact 4.2 billion years ago that may have formed the Serenitatis Basin
- 2021
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Ingår i: Communications Earth & Environment. - : Springer Science and Business Media LLC. - 2662-4435. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Impact cratering on the Moon and the derived size-frequency distribution functions of lunar impact craters are used to determine the ages of unsampled planetary surfaces across the Solar System. Radiometric dating of lunar samples provides an absolute age baseline, however, crater-chronology functions for the Moon remain poorly constrained for ages beyond 3.9 billion years. Here we present U–Pb geochronology of phosphate minerals within shocked lunar norites of a boulder from the Apollo 17 Station 8. These minerals record an older impact event around 4.2 billion years ago, and a younger disturbance at around 0.5 billion years ago. Based on nanoscale observations using atom probe tomography, lunar cratering records, and impact simulations, we ascribe the older event to the formation of the large Serenitatis Basin and the younger possibly to that of the Dawes crater. This suggests the Serenitatis Basin formed unrelated to or in the early stages of a protracted Late Heavy Bombardment.
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| 28. |
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| 29. |
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| 30. |
- Ioannou, Nikolaos, et al.
(författare)
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Triggering interferon signaling in T cells with avadomide sensitizes CLL to anti-PD-L1 /PD-1 immunotherapy
- 2021
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 137:2, s. 216-231
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Tidskriftsartikel (refereegranskat)abstract
- Cancer treatment has been transformed by checkpoint blockade therapies, with the highest anti-tumor activity of anti-programmed death 1 (PD-1) antibody therapy seen in Hodgkin lymphoma. Disappointingly, response rates have been low in the non-Hodgkin lymphomas, with no activity seen in relapsed/refractory chronic lymphocytic leukemia (CLL) with PD-1 blockade. Thus, identifying more powerful combination therapy is required for these patients. Here, we preclinically demonstrate enhanced anti-CLL activity following combinational therapy with anti-PD-1 or anti-PD-1 ligand (PD-L1) and avadomide, a cereblon E3 ligase modulator (CELMoD). Avadomide induced type I and II interferon (IFN) signaling in patient T cells, triggering a feedforward cascade of reinvigorated T-cell responses. Immune modeling assays demonstrated that avadomide stimulated T-cell activation, chemokine expression, motility and lytic synapses with CLL cells, as well as IFN-inducible feedback inhibition through upregulation of PD-L1. Patient-derived xenograft tumors treated with avadomide were converted to CD8(+) T cell-inflamed tumor microenvironments that responded to anti-PD-L1/PD-1-based combination therapy. Notably, clinical analyses showed increased PD-L1 expression on T cells, as well as intratumoral expression of chemokine signaling genes in B-cell malignancy patients receiving avadomide-based therapy. These data of overcoming a low inflammatory T-cell state to successfully sensitize CLL to checkpoint illustrate the importance blockade-based combination therapy.
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| 31. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 32. |
- Kazadi Mbamba, Christian, et al.
(författare)
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Plant-wide model-based analysis of iron dosage strategies for chemical phosphorus removal in wastewater treatment systems
- 2019
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Ingår i: Water Research. - : Elsevier BV. - 0043-1354 .- 1879-2448. ; 155, s. 12-25
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Tidskriftsartikel (refereegranskat)abstract
- Stringent phosphorus discharge standards (i.e. 0.15–0.3 g P.m −3 ) in the Baltic area will compel wastewater treatment practice to augment enhanced biological phosphorus removal (EBPR) with chemical precipitation using metal salts. This study examines control of iron chemical dosing for phosphorus removal under dynamic loading conditions to optimize operational aspects of a membrane biological reactor (MBR) pilot plant. An upgraded version of the Benchmark Simulation Model No. 2 (BSM2) with an improved physico-chemical framework (PCF) is used to develop a plant-wide model for the pilot plant. The PCF consists of an equilibrium approach describing ion speciation and pairing, kinetic minerals precipitation (such as hydrous ferric oxides (HFO) and FePO 4 ) as well as adsorption and co-precipitation. Model performance is assessed against data sets from the pilot plant, evaluating the capability to describe water and sludge lines across the treatment process under steady-state operation. Simulated phosphorus differed as little as 5–10% (relative) from measured phosphorus, indicating that the model was representative of reality. The study also shows that environmental factors such as pH, as well operating conditions such as Fe/P molar ratios (1, 1.5 and 2), influence the concentration of dissolved phosphate in the effluent. The time constant of simultaneous precipitation in the calibrated model, due to a step change decrease/increase in FeSO 4 dosage, was found to be roughly 5 days, indicating a slow dynamic response due to a multi-step process involving dissolution, oxidation, precipitation, aging, adsorption and co-precipitation. The persistence effect of accumulated iron-precipitates (HFO particulates) in the activated sludge seemed important for phosphorus removal, and therefore solids retention time plays a crucial role according to the model. The aerobic tank was deemed to be the most suitable dosing location for FeSO 4 addition, due to high dissolved oxygen levels and good mixing conditions. Finally, dynamic model-based analyses show the benefits of using automatic control when dosing chemicals. © 2019 Elsevier Ltd
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| 33. |
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| 34. |
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| 35. |
- Perry, D., et al.
(författare)
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FEIBA prophylaxis in haemophilia patients: a clinical update and treatment recommendations
- 2010
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 16:1, s. 80-89
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Tidskriftsartikel (refereegranskat)abstract
- In patients with severe haemophilia and inhibitors, regular factor VIII inhibitor bypassing activity (FEIBA) prophylaxis has been shown to reduce the frequency of bleeding by up to 85% and to improve patient quality of life. FEIBA is well tolerated; the incidence of thrombotic events and of allergic reactions is extremely low. The concept of prophylaxis in haemophilia patients with inhibitors is relatively new and some clinicians may be unsure of how to use FEIBA in this context. These treatment recommendations, based on published evidence plus the collective experience of a group of haematologists (with practical knowledge of managing inhibitor patients with FEIBA prophylaxis), are intended to provide guidance to clinicians considering initiating and maintaining patients on FEIBA prophylaxis with specific focus on practical aspects of patient selection, dosing, monitoring and stop criteria.
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| 36. |
- Tait, Brian D, et al.
(författare)
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Consensus Guidelines on the Testing and Clinical Management Issues Associated With HLA and Non-HLA Antibodies in Transplantation.
- 2013
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Ingår i: Transplantation. - 1534-6080. ; 95:1, s. 19-47
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The introduction of solid-phase immunoassay (SPI) technology for the detection and characterization of human leukocyte antigen (HLA) antibodies in transplantation while providing greater sensitivity than was obtainable by complement-dependent lymphocytotoxicity (CDC) assays has resulted in a new paradigm with respect to the interpretation of donor-specific antibodies (DSA). Although the SPI assay performed on the Luminex instrument (hereafter referred to as the Luminex assay), in particular, has permitted the detection of antibodies not detectable by CDC, the clinical significance of these antibodies is incompletely understood. Nevertheless, the detection of these antibodies has led to changes in the clinical management of sensitized patients. In addition, SPI testing raises technical issues that require resolution and careful consideration when interpreting antibody results. METHODS: With this background, The Transplantation Society convened a group of laboratory and clinical experts in the field of transplantation to prepare a consensus report and make recommendations on the use of this new technology based on both published evidence and expert opinion. Three working groups were formed to address (a) the technical issues with respect to the use of this technology, (b) the interpretation of pretransplantation antibody testing in the context of various clinical settings and organ transplant types (kidney, heart, lung, liver, pancreas, intestinal, and islet cells), and (c) the application of antibody testing in the posttransplantation setting. The three groups were established in November 2011 and convened for a "Consensus Conference on Antibodies in Transplantation" in Rome, Italy, in May 2012. The deliberations of the three groups meeting independently and then together are the bases for this report. RESULTS: A comprehensive list of recommendations was prepared by each group. A summary of the key recommendations follows. Technical Group: (a) SPI must be used for the detection of pretransplantation HLA antibodies in solid organ transplant recipients and, in particular, the use of the single-antigen bead assay to detect antibodies to HLA loci, such as Cw, DQA, DPA, and DPB, which are not readily detected by other methods. (b) The use of SPI for antibody detection should be supplemented with cell-based assays to examine the correlations between the two types of assays and to establish the likelihood of a positive crossmatch (XM). (c) There must be an awareness of the technical factors that can influence the results and their clinical interpretation when using the Luminex bead technology, such as variation in antigen density and the presence of denatured antigen on the beads. Pretransplantation Group: (a) Risk categories should be established based on the antibody and the XM results obtained. (b) DSA detected by CDC and a positive XM should be avoided due to their strong association with antibody-mediated rejection and graft loss. (c) A renal transplantation can be performed in the absence of a prospective XM if single-antigen bead screening for antibodies to all class I and II HLA loci is negative. This decision, however, needs to be taken in agreement with local clinical programs and the relevant regulatory bodies. (d) The presence of DSA HLA antibodies should be avoided in heart and lung transplantation and considered a risk factor for liver, intestinal, and islet cell transplantation. Posttransplantation Group: (a) High-risk patients (i.e., desensitized or DSA positive/XM negative) should be monitored by measurement of DSA and protocol biopsies in the first 3 months after transplantation. (b) Intermediate-risk patients (history of DSA but currently negative) should be monitored for DSA within the first month. If DSA is present, a biopsy should be performed. (c) Low-risk patients (nonsensitized first transplantation) should be screened for DSA at least once 3 to 12 months after transplantation. If DSA is detected, a biopsy should be performed. In all three categories, the recommendations for subsequent treatment are based on the biopsy results. CONCLUSIONS: A comprehensive list of recommendations is provided covering the technical and pretransplantation and posttransplantation monitoring of HLA antibodies in solid organ transplantation. The recommendations are intended to provide state-of-the-art guidance in the use and clinical application of recently developed methods for HLA antibody detection when used in conjunction with traditional methods.
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| 37. |
- Tait, S, et al.
(författare)
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Italian Children Exposure to Bisphenol A: Biomonitoring Data from the LIFE PERSUADED Project
- 2021
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 18:22
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Tidskriftsartikel (refereegranskat)abstract
- A human biomonitoring (HBM) study on bisphenol A (BPA) in Italian children and adolescents was performed within the LIFE PERSUADED project, considering the residing areas, sex and age. The median urinary BPA level was 7.02 µg/L, with children living in the South of Italy or in urban areas having higher levels than those residing in the North or in rural areas. Children aged 4–6 years had higher BPA levels than those aged 7–10 and 11–14 years, but no differences were detected between sexes. The exposure in Italian children was higher compared to children from other countries, but lower than the HBM guidance value (135 µg/L). The estimated daily intake was 0.17 μg/kg body weight (bw) per day, about 24-fold below the temporary Tolerable Daily Intake of 4 μg/kg bw per day established by the European Food Safety Authority. However, this threshold was exceeded in 1.44% of the enrolled children, raising concern about the overall exposure of Italian young population.
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