| 1. |
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| 2. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 3. |
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| 4. |
- Nikpay, Majid, et al.
(författare)
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A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:10, s. 1121-1121
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Tidskriftsartikel (refereegranskat)abstract
- Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
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| 5. |
- Snygg-Martin, Ulrika, 1965, et al.
(författare)
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Cerebrovascular complications in patients with left-sided infective endocarditis are common: a prospective study using magnetic resonance imaging and neurochemical brain damage markers.
- 2008
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Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 47:1, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Background. @nbsp; Cerebrovascular complications (CVCs) have remained a major therapeutic and prognostic challenge associated with infective endocarditis, and definite risk factors have not been fully elucidated. This prospective study was designed to the evaluate the total incidence of CVC associated with infective endocarditis and major risk factors. Methods. @nbsp; During 2 study periods, from June 1998 through April 2001 and from September 2002 through January 2005, patients were prospectively enrolled in the study regardless of neurological symptoms. Study patients underwent neurological examinations and magnetic resonance imaging of the brain, and cerebrospinal fluid analyses of inflammatory and neurochemical markers of brain damage (neurofilament protein and glial fibrillary acidic protein) were performed. Results. @nbsp; Sixty patients who experienced episodes of left-sided infective endocarditis were evaluated; 35% of these patients experienced a symptomatic CVC. Silent cerebral complications were detected in another 30% of the patients, and the total CVC rate was 65% (95% confidence interval, 58%-72%). Five percent of patients experienced their first neurological symptom after the initiation of antibiotic treatment without prior surgery. No new symptomatic CVCs were detected after 10 days of antibiotic treatment. No neurological deterioration was observed after surgery in patients who were established to have a symptomatic CVC preoperatively. A larger heart valvular vegetation size was a risk factor for both symptomatic and silent CVCs; Staphylococcus aureus etiology conferred a higher risk for symptomatic cerebral complication only. Conclusions. @nbsp; The use of sensitive methods of detection indicates that the incidence of CVC associated with infective endocarditis is high, but the risk for neurological deterioration during cardiac surgery after a CVC is lower than previously assumed. The major mechanism behind cerebral complications associated with infective endocarditis is cerebral embolization, although the dominant neurological symptoms vary considerably.
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| 6. |
- Strawbridge, Rona J., et al.
(författare)
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Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation
- 2017
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 266, s. 196-204
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling.Methods: We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants.Results: We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures.Conclusions: We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT.
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| 7. |
- Wernersson, Lars-Erik, et al.
(författare)
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Epitaxially overgrown, stable W-GaAs Schottky contacts with sizes down to 50 nm
- 2002
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Ingår i: Journal of Vacuum Science and Technology B. - : American Vacuum Society. - 1520-8567. ; 20:2, s. 580-589
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Tidskriftsartikel (refereegranskat)abstract
- A processing scheme for the fabrication of embedded W-GaAs contacts has been established and the resulting contact characteristics have been evaluated. The main advantage of these contacts is that they are stable during high-temperature epitaxial overgrowth. The fabrication scheme is based on a liftoff process with electron beam evaporation of tungsten and subsequent epitaxial overgrowth using metalorganic vapor phase epitaxy. Various methods were used to characterize the buried contacts. First, the structural properties of GaAs surrounding embedded W features, with widths down to 50 nm, were characterized by high-resolution transmission electron microscopy. Measurements of the conductivity in individual, buried wires were performed in order to study the influence of the overgrowth process on the properties of the tungsten. We also evaluated the current-voltage characteristics for macroscopic contacts, which revealed a clear dependence on processing parameters. Optimized processing conditions could thus be established under which limited contact degradation occurred during overgrowth. Finally, we used the overgrowth technique to perform a detailed investigation of the electrical and optical properties of floating-potential embedded nano-Schottky contacts by space-charge spectroscopy.
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| 8. |
- Annika, Hagenbjörk-Gustafsson, et al.
(författare)
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Spatial variation of ground level ozone and the relation between ozone and NO2/NOx in two Swedish cities
- 2013
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Konferensbidrag (refereegranskat)abstract
- Background Ozone is a pollutant known to cause adverse effects on human health. It is formed by reactions between nitrogen oxides (NOx) and hydrocarbons under the influence of sunlight. In urban areas ozone is consumed oxidating nitrogen oxide (NO) to nitrogen dioxide (NO2). Despite the potential to cause adverse health effects, the local spatial distribution of ozone and the relationship between ozone, NO2 and NOx in different environments is poorly studied.Aims Our aim was to study the concentrations and spatial distribution of ozone in two cities, Malmö in the south of Sweden and Umeå in the north of Sweden, since the contribution of ozone from other parts of Europe decreases with higher latitude. We also wanted to investigate differences in the ozone/NO2 and the ozone/NOx ratios between the cities and between different environments.Methods Ozone, NO2 and NOx concentrations were measured with Ogawa diffusive samplers during three one-week campaigns in April, May/June and in August 2012. Measurements were conducted simultaneously at 20 sites in each city outside preschools, distributed at traffic sites, urban background sites and regional background (rural) sites. Results The average concentration of ozone in Malmö and Umeå were 67,5 µg/m3 and 50,6 µg/m3, respectively. The mean ozone/NOx ratio was of equal magnitude in Malmö and in Umeå, and in both cities the ratio was highest at rural sites and lowest at traffic sites. In Umeå there was a clear trend with highest ozone concentrations at rural sites and lowest concentrations at traffic sites, a trend that was not as obvious in Malmö. In Umeå the ozone/NO2 ratio at rural sites was about three times larger compared to Malmö.Conclusions There is a clear local variation of ozone, with stronger gradients in northern (Umeå) Sweden in comparison to southern Sweden (Malmö). This can partly be explained by less long-range transport of ozone and larger impact of local NO emissions that reduce ozone in northern Sweden.
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| 9. |
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| 10. |
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| 11. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 12. |
- Dalmar, Abdirisak Ahmed, et al.
(författare)
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Rebuilding research capacity in fragile states : the case of a Somali-Swedish global health initiative
- 2017
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Ingår i: Global Health Action. - Abingdon : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents an initiative to revive the previous Somali-Swedish Research Cooperation, which started in 1981 and was cut short by the civil war in Somalia. A programme focusing on research capacity building in the health sector is currently underway through the work of an alliance of three partner groups: six new Somali universities, five Swedish universities, and Somali diaspora professionals. Somali ownership is key to the sustainability of the programme, as is close collaboration with Somali health ministries. The programme aims to develop a model for working collaboratively across regions and cultural barriers within fragile states, with the goal of creating hope and energy. It is based on the conviction that health research has a key role in rebuilding national health services and trusted institutions.
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| 13. |
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| 14. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 15. |
- Folkersen, Lasse, et al.
(författare)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 16. |
- Gustafsson, Bengt I., 1955, et al.
(författare)
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Retransplantation of the liver.
- 2006
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Ingår i: Transplantation proceedings. - : Elsevier BV. - 0041-1345. ; 38:5, s. 1438-9
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Tidskriftsartikel (refereegranskat)abstract
- Retransplantation (re-TX) is the only available therapy for irreversible liver graft dysfunction. The outcome of a second procedure depends upon several factors, some of which are not defined at the time of the decision to retransplant. This study is an analysis of all re-TX of the liver performed at our unit between January 1995 and January 2004. Among the 474 liver TX were 55 (11.6%) re-TX in 47 patients. We studied (1) diagnosis at first TX; (2) indication for re-TX and time lapse; (3) donor age and cold ischemia time (CIT); (4) duration of operation, peroperative bleeding, and complications; (5) ICU and ward periods; and (6) patient and graft survivals. Patients who underwent re-TX did not differ from those transplanted once with regard to age, gender, or diagnosis. The indications for re-TX were roughly one-third biliary tract complications/chronic rejection, one-third hepatic artery thrombosis, and one-third others, including primary nonfunction, acute rejection, portal vein thrombosis, sepsis, and B/C hepatitis. The re-TX were "urgent" in 29 and "elective" in 26 cases. Complications were common; about half of the patients were reoperated due to bleeding or biliary problems. To date (May 2004), 15 patients have died (12 "urgent" and 3 "elective"), of whom 5 had well functioning grafts. In summary, liver re-TX is a complicated procedure associated with significant mortality and morbidity, but considering that the actual patient group has a poor prognosis without re-TX, the results are nevertheless encouraging.
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| 17. |
- Gustafsson, Lars, 1950, et al.
(författare)
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Adults and mathematics - a vital subject
- 2004
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- The National Center for Mathematics Education (NCM) was commissioned in October 2001 by the Swedish Government to carry out a survey and produce an analysis of the measures required to improve adult learning of mathematics. The results of this assignment were presented in June 2002 in the swedish report Vuxna och matematik - ett livsviktigt ämne (NCM Report 2002:3).
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| 18. |
- Gustafsson, Lars L., et al.
(författare)
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The 'wise list'- a comprehensive concept to select, communicate and achieve adherence to recommendations of essential drugs in ambulatory care in Stockholm
- 2011
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - Copenhagen : Blackwell Publishing. - 1742-7835 .- 1742-7843. ; 108:4, s. 224-233
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to present and evaluate the impact of a comprehensive strategy over 10 years to select, communicate and achieve adherence to essential drug recommendations (EDR) in ambulatory care in a metropolitan healthcare region. EDRs were issued and launched as a 'Wise List' by the regional Drug and Therapeutics Committee in Stockholm. This study presents the concept by: (i) documenting the process for selecting, communicating and monitoring the impact of the 'Wise List'; (ii) analysing the variation in the number of drug substances recommended between 2000 and 2010; (iii) assessing the attitudes to the 'Wise List' among prescribers and the public; (iv) evaluating the adherence to recommendations between 2003 and 2009. The 'Wise List' consistently contained 200 drug substances for treating common diseases. The drugs were selected based on their efficacy, safety, suitability and cost-effectiveness. The 'Wise List' was known among one-third of a surveyed sample of the public in 2002 after initial marketing campaigns. All surveyed prescribers knew about the concept and 81% found the recommendations trustworthy in 2005. Adherence to recommendations increased from 69% in 1999 to 77% in 2009. In primary care, adherence increased from 83% to 87% from 2003 to 2009. The coefficient of variation (CV%) decreased from 6.1% to 3.8% for 156 healthcare centres between these years. The acceptance of the 'Wise List' in terms of trust among physicians and among the public and increased adherence may be explained by clear criteria for drug recommendations, a comprehensive communication strategy, electronic access to recommendations, continuous medical education and involvement of professional networks and patients.
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| 19. |
- Gustafsson, Lars, 1950, et al.
(författare)
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Matematik för vuxna
- 2002
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Ingår i: Nämnaren. - 0348-2723. ; :2002:4, s. 40-43
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- I denna artikel beskrivs rapporten, Vuxna och matematik ett livsviktigt ämne, där vuxnas matematiklärande på grundskole- och gymnasienivå är i fokus.
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| 20. |
- Gustafsson, Lars, 1950, et al.
(författare)
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Mathematical modelling and tacit rationality - two intertwining kinds of professional knowledge
- 2010
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Ingår i: EIMI 2010 : Educational Interfaces between Mathematics and Industry : proceedings. ; , s. 253-268
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Konferensbidrag (refereegranskat)abstract
- In this paper the view that mathematical practice always is applications of mathematical models is problematized. We argue that there is a tacit rationality, with a broader qualitative mathematical essence, that has another origin, and another character and function. This kind of rationality is bound to personal practice and our bodily interactions with the outside world. It is also bridging the gulf between the generality of the applied general mathematical model and the specific concrete acting in the material situation. For validation of the skilled and experienced worker the traditional school based tests of mathematical knowledge are therefore misleading and often contra-productive, and a depreciation of a workers professional skills. Validation settings in order to evaluate for instance vocational education and adults further education efforts should have a much broader repertoire to make this kind of knowledge visible and evaluable. There is also a need to problematize the definition of mathematical acting. By school tradition the pencil and paper activities has been the only “legal” means to show your mathematical capacity. This poor environment has been supposed to be context-free, but we argue it has its own context, and is often a doubtful preparation for future working life.
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| 21. |
- Gustafsson, Lena, et al.
(författare)
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Rapid ecological response and intensified knowledge accumulation following a north European mega-fire
- 2019
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Ingår i: Scandinavian Journal of Forest Research. - : Informa UK Limited. - 0282-7581 .- 1651-1891. ; 34:4, s. 234-253
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Forskningsöversikt (refereegranskat)abstract
- Deepened knowledge on response of biota and ecological processes following fire is essential for a future with warmer climate and more disturbances. In 2014 the first mega-fire (13,100 ha) for at least a century in Scandinavia hit south-central Sweden, in a production forest landscape shaped by clearcutting forestry. Ecological dynamics is followed in >20 projects from universities, authorities and citizen science initiatives, rapidly accumulating substantial amounts of data. We outline projects and summarize their results during the first four years, demonstrating a rapid succession of fungi, lichens, vascular plants, birds, mammals, ticks, butterflies, beetles, and drastically altered carbon dynamics. We characterize forest operations including regeneration measures and point to patterns in pest and pathogen infestations. 8,000 ha is set aside for natural succession, with the rest harvested and managed for forest production, offering excellent opportunities for studies on salvage logging effects, already evident for birds. We demonstrate a strong regrowth of deciduous trees, and the protected part will in some decades likely develop into the largest deciduous-dominated area in boreal north Europe outside Russia. Continued studies of biodiversity and ecological processes are urgent for this unique area.
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| 22. |
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| 23. |
- Gustafsson, Lars, 1950, et al.
(författare)
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Validation of adults' proficiency - fairness in focus
- 2008
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- In the report, which should be regarded as a position paper, the authors have analysed and reviewed the problems connected to validation from a number of different perspectives. They have also tried to achieve a synthesis of the ideas and aspects which they believe are essential for developing more concrete methods for organising validation. Their analysis builds on the findings of research from different theoretical approaches, disciplines and traditions, and on policy documents concerning adult learning, as well as many years of personal experience from adult education. The synthesis also reflects an approach to the individual and to knowledge, and thus has an ethical as well as an epistemological dimension.
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| 24. |
- Gustafsson, Lars, 1950, et al.
(författare)
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Validering - att göra den vuxne rättvisa
- 2008
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Ingår i: Nämnaren. - 0348-2723. ; :2008:1, s. 27-30
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Måste matematikanvändning alltid vara tillämpning av en formaliserad matematisk modell eller kan denna användning ha en helt annan karaktär, oupplösligt inbäddad i ett praktiskt görande? Hur ska man i så fall kunna validera den vuxnes matematiska kunnande? Ett skolbänkstest med papper och penna kan knappast räcka till.
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| 25. |
- Gustafsson, Lars, 1950, et al.
(författare)
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Validering av vuxnas kunnande - med rättvisa i fokus
- 2008
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Om olika former av vuxnas kunnande och hur dessa gestaltas i olika uttryckssätt. Komplexiteten av frågeställningar som är aktuella inför en valideringsprocess.
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| 26. |
- Gustafsson, Lars, 1950, et al.
(författare)
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Vuxna och matematik - ett livsviktigt ämne
- 2002
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Vuxnas matematiklärande diskuteras utifrån ett antal motivbilder såsom individ och samhälle, demokrati och värdegrund, det livslånga och livsvida lärandet, lärande och kunskap i kunskapssamhället, vägledning och validering. En problematiserande beskrivning av vad (skol-)matematik är och vad "baskunnande för alla" kan innebära utgör centrala avsnitt i rapporten.
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| 27. |
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| 28. |
- Johansson, Lars-Olof, 1957, et al.
(författare)
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Weighing third-party fairness, efficiency, and self-interest in resource allocation decisions
- 2007
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Ingår i: Journal of Economic Psychology. ; , s. 53-68
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Tidskriftsartikel (refereegranskat)abstract
- In two experiments participants allocated a resource between themselves, one privileged, and one unprivileged group. Conflicts were induced between “third party fairness” (difference in payoff to the two groups) and efficient resource use. Experiment 1 employed 42 undergraduates making multi-stage allocation decisions. Fairness was varied at three levels and self-interest, operationalized as the political motive of win votes, at two levels. Adverse effects of fairness on preserving the resource were found. In Experiment 2 another 48 undergraduates performed a similar task. Self-interest was now operationalized as a financial motive. The results showed that participants reduced their resource use when neither fairness nor self-interest was salient. A regression analysis demonstrated consistent adverse effects of fairness on resource use controlling for efficient resource use and total group payoff. It was concluded that fairness causes decision makers to overuse resources, although they are unwilling to totally deplete a resource and will make compromises.
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| 29. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 30. |
- Karlsson, Lars O, 1975, et al.
(författare)
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Opioid receptor agonist Eribis peptide 94 reduces infarct size in different porcine models for myocardial ischaemia and reperfusion
- 2011
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 651:1-3, s. 146-151
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Tidskriftsartikel (refereegranskat)abstract
- Eribis peptide 94 (EP 94) is a novel enkephalin analog, thought to interact with the and delta-opioid receptors. The purpose of the present study was to examine the cardioprotective potential of EP 94 in two clinically relevant porcine models of myocardial ischaemia and reperfusion, and to investigate if such an effect is associated with an increased expression of endothelial nitric oxide synthase (eNOS). Forty-one anesthetized pigs underwent 40 min of coronary occlusion followed by 4 h of reperfusion. In Protocol I, balloon occlusion of the left anterior descending artery was performed with concurrent intravenous administration of (A) vehicle (n = 7), (B) EP 94 (1 ug/kg) after 5, 12, 19 and 26 min of ischaemia (n = 4) or (C) EP 94 (1 ug/kg) after 26, 33, 40 min of ischaemia (n = 6). In Protocol II, open-chest pigs were administered (D) vehicle (n = 6) or (E) 0.2 ug/kg/min of EP 94 (n = 6) through an intracoronary infusion into the jeopardized myocardium, started after 30 min of ischaemia and maintained for 15 min. The hearts were stained and the protein content of eNOS measured. EP 94 reduces infarct size when administered both early and late during ischaemia compared with vehicle (infarct size group A 61.6 +/- 2%, group B 50.2 +/- 3% and group C 49.2 +/- 2%, respectively, P < 0.05), as well as when infused intracoronary (infarct size group D 82.2 +/- 3.9% and group E 61.2 +/- 2.5% respectively, P < 0.01). Phosphorylated eNOS Ser(I177) in relation to total eNOS was significantly increased in the group administered EP 94. indicating activation of nitric oxide production.
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| 31. |
- Klaric, Lucija, et al.
(författare)
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Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
- 2021
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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| 32. |
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| 33. |
- Ljungman, Gustaf, et al.
(författare)
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Incidence and Survival Analyses in Children with Solid Tumours Diagnosed in Sweden 1983-2007.
- 2011
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Ingår i: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 100:5, s. 750-757
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Solid tumours constitute 40% of childhood malignancies. The Swedish Childhood Cancer Registry is population-based and includes all children with cancer reported from the six paediatric oncology centres in Sweden. The aim was to investigate incidence and survival. Methods: We used the new WHO ICCC-3 for reclassification of the patients. Incidence and survival analyses were performed in the study population. Results: 2 487 children (< 15 years) were diagnosed with solid tumours in Sweden 1983 - 2007. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 65.3/million children. The survival rates at 10 years follow up have improved significantly when comparing the two time periods 1983-95 and 1995-2007 (76 vs. 82%; p<0.01). Conclusions: The mean annual incidence of solid tumours in children was 65.3/ million and has been stable during the study period. Survival rates for solid tumours at 5, 10 and 20 years follow up were 80, 79 and 76%, respectively.
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| 34. |
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| 35. |
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| 36. |
- Ljungman, Gustaf, et al.
(författare)
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Incidence and survival analyses in children with solid tumours diagnosed in Sweden between 1983 and 2007
- 2011
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 100:5, s. 750-757
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Solid tumours constitute 40% of childhood malignancies. The Swedish Childhood Cancer Registry is population based and includes all children with cancer reported from the six paediatric oncology centres in Sweden. The aim was to investigate incidence and survival. Methods: We used the new WHO ICCC-3 for reclassification of the patients. Incidence and survival analyses were performed in the study population. Results: Two thousand four hundred and eighty-seven children (< 15 years) were diagnosed with solid tumours in Sweden between 1983 and 2007. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 65.3 per million children. The survival rates at 10 years of follow-up have improved significantly when comparing the two time periods, 1983-1995 and 1995-2007 (76 vs. 82%; p < 0.01). Conclusions: The mean annual incidence of solid tumours in children was 65.3/million and has been stable during the study period. Survival rates for solid tumours at 5, 10 and 20 years follow-up were 80, 79 and 76%, respectively.
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| 37. |
- Lu, Jun, et al.
(författare)
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Inhibition of Bacterial Thioredoxin Reductase: An Antibiotic Mechanism Targetting Bacteria Lacking Glutathione
- 2013
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 27:4, s. 1394-1403
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Tidskriftsartikel (refereegranskat)abstract
- Increasing antibiotic resistance makes the identification of new antibacterial principles an urgent task. The thioredoxin system including thioredoxinreductase (TrxR), thioredoxin (Trx), and NADPH plays critical roles in cellular DNA synthesis and defense against oxidative stress. Notably, TrxR is very different in structure and mechanism in mammals and bacteria. Ebselen [2-phenyl-1,2 benzisoselenazol-3(2H)-one], a well-known antioxidant and a substrate for mammalian TrxR and Trx, is rapidly bacteriocidal for methicillin-resistant Staphylococcus aureus by an unknown mechanism. We have discovered that ebselen is a competitive inhibitor of Escherichia coli TrxR with a K-i of 0.52 +/- 0.13 mu M, through reaction with the active site dithiol of the enzyme. Bacteria lacking glutathione (GSH) and glutaredoxin, in which TrxR and Trx are essential for DNA synthesis, were particularly sensitive to ebselen. In growth-inhibited E. coli strains, Trx1 and Trx2 were oxidized, demonstrating that electron transfer via thioredoxin was blocked. Ebselen and its sulfur analog ebsulfur were bactericidal for GSH-negative pathogens. Ebsulfur inhibited a clinically isolated Helicobacter pylori strain with a minimum inhibitory concentration value as low as 0.39 mu g/ml. These results demonstrate that bacterial Trx and TrxR are viable antibacterial drug targets using benzisoselenazol and benzisothiazol derivates.-Lu, J., Vlamis-Gardikas, A., Kandasamy, K., Zhao, R., Gustafsson, T. N., Engstrand, L., Hoffner, S., Engman, L., Holmgren, A. Inhibition of bacterial thioredoxin reductase: an antibiotic mechanism targeting bacteria lacking glutathione.
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| 38. |
- Lu, Yingchang, et al.
(författare)
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New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
- 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
- To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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| 39. |
- Lundström, Emeli, et al.
(författare)
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HLA-DRB1*04/*13 alleles are associated with vascular disease and antiphospholipid antibodies in systemic lupus erythematosus
- 2013
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 72:6, s. 1018-1025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES:Vascular disease is common in systemic lupus erythematosus (SLE) and patients with antiphospholipid antibodies (aPL) are at high risk to develop arterial and venous thrombosis. Since HLA class II genotypes have been linked to the presence of pro-thrombotic aPL, we investigated the relationship between HLA-DRB1 alleles, aPL and vascular events in SLE patients.METHODS:665 SLE patients of Caucasian origin and 1403 controls were included. Previous manifestations of ischaemic heart disease, ischaemic cerebrovascular disease (ICVD) and venous thromboembolism (together referred to as any vascular events (AVE)) were tabulated. aPL were measured with ELISA. Two-digit HLA-DRB1 typing was performed by sequence-specific primer-PCR.RESULTS: HLA-DRB1*04 was more frequent among SLE patients with ICVD compared to unaffected patients. This association remained after adjustment for known traditional cardiovascular risk factors. HLA-DRB1*13 was associated with AVE. All measured specificities of aPL—cardiolipin IgG and IgM, β2-glycoprotein-1 IgG, prothrombin (PT) IgG and a positive lupus anticoagulant test were associated with HLA-DRB1*04—while HLA-DRB1*13 was associated with IgG antibodies (β2-glycoprotein-1, cardiolipin and PT). In patients with the combined risk alleles, HLA-DRB1*04/*13, there was a significant additive interaction for the outcomes AVE and ICVD.CONCLUSIONS:The HLA-DRB1*04 and HLA-DRB1*13 alleles are associated with vascular events and an aPL positive immune-phenotype in SLE. Results demonstrate that a subset of SLE patients is genetically disposed to vascular vulnerability.
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| 40. |
- Malmqvist, Ebba, et al.
(författare)
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Assessing ozone exposure for epidemiological studies in Malmo and Umea, Sweden
- 2014
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 94, s. 241-248
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Tidskriftsartikel (refereegranskat)abstract
- Ground level ozone [ozone] is considered a harmful air pollutant but there is a knowledge gap regarding its long term health effects. The main aim of this study is to develop local Land Use Regression [LUR] models that can be used to study long term health effects of ozone. The specific aim is to develop spatial LUR models for two Swedish cities, Umea and Malmo, as well as a temporal model for Malmo in order to assess ozone exposure for long term epidemiological studies. For the spatial model we measured ozone, using Ogawa passive samplers, as weekly averages at 40 sites in each study area, during three seasons. This data was then inserted in the LUR-model with data on traffic, land use, population density and altitude to develop explanatory models of ozone variation. To develop the temporal model for Malmo, hourly ozone data was aggregated into daily means for two measurement stations in Malmo and one in a rural area outside Malmo. Using regression analyses we inserted meteorological variables into different temporal models and the one that performed best for all three stations was chosen. For Malmo the LUR-model had an adjusted model R-2 of 0.40 and cross validation R-2 of 0.17. For Umea the model had an adjusted model R-2 of 0.67 and cross validation adjusted R-2 of 0.48. When restricting the model to only including measuring sites from urban areas, the Malmo model had adjusted model R-2 of 0.51 (cross validation adjusted R-2 0.33) and the Umea model had adjusted model R-2 of 0.81 (validation adjusted R-2 of 0.73). The temporal model had adjusted model R-2 0.54 and 0.61 for the two Malmo sites, the cross validation adjusted R-2 was 0.42. In conclusion, we can with moderate accuracy, at least for Umea, predict the spatial variability, and in Malmo the temporal variability in ozone variation. (C) 2014 The Authors. Published by Elsevier Ltd.
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| 41. |
- Mouwitz, Lars, 1949, et al.
(författare)
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Adults and mathematics - a vital subject
- 2004
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Ingår i: Lindberg, Lisbeth (red.). "Bildning" and/or training. Proceedings of the 11th International Conference on Adult Learning Mathematics in Kungälv (Göteborg, Sweden) 29th June to 2nd July 2004. (ALM 11). ; , s. 42-49
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Konferensbidrag (refereegranskat)
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| 42. |
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| 43. |
- Schmidt, Amand F., et al.
(författare)
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PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study
- 2017
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Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:2, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibitor treatment, as was previously done for statins.
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| 44. |
- Schmidt, Amand F., et al.
(författare)
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Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
- 2019
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Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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| 45. |
- Scott, Robert A., et al.
(författare)
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An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:11, s. 2888-2902
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Tidskriftsartikel (refereegranskat)abstract
- To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 x 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
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| 46. |
- Sizov, Andrey, 1989, et al.
(författare)
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Thermal conductivity versus depth profiling of inhomogeneous materials using the hot disc technique
- 2016
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 1089-7623 .- 0034-6748. ; 87:7, s. 074901-
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Tidskriftsartikel (refereegranskat)abstract
- Transient measurements of thermal conductivity are performed with hot disc sensors on samples having a thermal conductivity variation adjacent to the sample surface. A modified computational approach is introduced, which provides a method of connecting the time-variable to a corresponding depth-position. This allows highly approximate—yet reproducible—estimations of the thermal conductivity vs. depth. Tests are made on samples incorporating different degrees of sharp structural defects at a certain depth position inside a sample. The proposed methodology opens up new possibilities to perform non-destructive testing; for instance, verifying thermal conductivity homogeneity in a sample, or estimating the thickness of a deviating zone near the sample surface (such as a skin tumor), or testing for presence of other defects
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| 47. |
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| 48. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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| 49. |
- Sonesten, Lars, et al.
(författare)
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Sources and pathways of nutrients to the Baltic Sea : HELCOM PLC-6
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Eutrophication caused by oversupply of the Baltic Sea by nutrients remains the major environmental pressure on the marine ecosystem. In order to mitigate eutrophication, HELCOM countries have agreed on a joint effort to reduce nutrient load on the marine ecosystem, reflected in the HELCOM Baltic Sea Action Plan as a nutrient input reduction scheme. Compilations of pollution load data, designed to follow up on the implementation of the scheme, have been an integral part of the HELCOM assessment system since 1987. This assessment of major sources and pathways of nitrogen and phosphorus into the marine environment is a vital part of the HELCOM Pollution Load Compilation (PLC) and one of the main products of the HELCOM Sixth Pollution Load Compilation project (PLC-6). The product includes an assessment of three major pathways of nutrients – riverine, airborne and via direct sources – and more detailed assessment of sources of riverine load.The previous (PLC-5) assessment, published in 2013, was based on the data on nutrient inputs in 2006. Current assessment illustrates the contribution of various sources of nitrogen and phosphorus into total loads in 2014 (2012 for Germany and Poland). The assessment also illustrates changes in proportion of different pathways since 1995.
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| 50. |
- Stockeld, Dag, et al.
(författare)
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A Swedish study of chemoradiation in squamous cell carcinoma of the esophagus
- 2001
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 40, s. 566-
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Tidskriftsartikel (refereegranskat)abstract
- This multicenter study describes the development of a chemoradiation protocol for the treatment of non-metastatic squamous cell carcinoma of the esophagus. Eighty patients were treated with three courses of chemotherapy (cisplatinum and 5-fluorouracil) with concomitant radiotherapy (40 Gy) during the last two courses of chemotherapy. Esophagectomy was performed, when feasible. If no operation was performed, patients were planned to receive a target dose of 64 Gy. Toxicity was mainly attributable to hematological impairment and led to two adjustments of the treatment protocol (addition of filgrastim and lowering of the 5-fluorouracil dose). These changes made it possible to administer the planned treatment in a gradually higher proportion of patients (13/23 [57%] before changes of treatment compared with 30/36 [83%] after changes). Treatment-related mortality was 3.75% (3 patients, associated with leucopenic septicemia after chemotherapy). Fifty-four patients were resected. No per- or postoperative mortality was encountered. The complete response (pathological CR) rate in operated patients was 46% (27/59 patients) after chemoradiation. In the whole series the CR rate (including clinical CR for non-resected patients) was 44%. With a minimum follow-up of 37 months, the 3-year survival for the whole group was 31% compared with 57% for the CR patients. Total 5-year survival thus far (July 1999) is 26%.
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