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- Simmen, K. A., et al.
(author)
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Macrocylic inhibitors of hepatitis C virus
- 2012
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Patent (pop. science, debate, etc.)abstract
- Inhibitors of HCV replication of formula (I)and the N-oxides, salts, and stereoisomers, whereineach dashed line represents an optional double bond;X is N, CH and where X bears a double bond it is C;R1 is —OR7, —NH—SO2R8;R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl;R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-7cycloalkyl;R4 is aryl or Het; n is 3, 4, 5, or 6;R5 is halo, C1-6alkyl, hydroxy, C1-6alkoxy, phenyl, or Het;R6 is C1-6alkoxy, or dimethylamino;R7 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het;R8 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het;aryl is phenyl optionally substituted with one, two or three substituents;Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three substituents;pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.
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- Ahlden, M., et al.
(author)
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Individualiserad terapi viktigt vid främre korsbandsskada
- 2014
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In: Läkartidningen. - : Swedish Medical Association. - 0023-7205 .- 1652-7518. ; 111:36, s. 1440-
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Journal article (peer-reviewed)abstract
- Anterior cruciate ligament (ACL) injury is a common injury and is often associated with concomitant injuries to the menisci and cartilage and, in the long term, osteoarthritis. Preventive training programs have shown to be highly effective in terms of reducing the risk for ACL injury in sports. ACL reconstruction is indicated when the patient experiences symtoms of instability (»giving way«) despite rehabilitation with a physiotherapist aiming to gain neuromuscular control of the knee. Early ACL reconstruction may be indicated, for example when the patient desires to return to pivoting contact-sports at high level. Modern surgical technique for ACL reconstruction has evolved rapidly and includes »anatomic reconstruction« and individualized treatment, where each patient’s unique anatomy, injury and requests on knee function are taken into consideration. In Sweden, more than 90% of all ACL reconstructions performed are included into the Swedish National ACL Register.
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- Jonsdottir, Berglind, et al.
(author)
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Thyroid autoimmunity in relation to islet autoantibodies and HLA-DQ genotype in newly diagnosed type 1 diabetes in children and adolescents
- 2013
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In: Diabetologia. - : Springer Verlag (Germany). - 0012-186X .- 1432-0428. ; 56:8, s. 1735-1742
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Journal article (peer-reviewed)abstract
- The aim of this work was to investigate, in children newly diagnosed with type 1 diabetes: (1) the prevalence of autoantibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb); and (2) the association between TPOAb, TGAb or both, with either islet autoantibodies or HLA-DQ genes. less thanbrgreater than less thanbrgreater thanBlood samples from 2,433 children newly diagnosed with type 1 diabetes were analysed for TPOAb and TGAb in addition to autoantibodies against arginine zinc transporter 8 (ZnT8RA), tryptophan zinc transporter 8 (ZnT8WA), glutamine zinc transporter 8 (ZnT8QA), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), HLA-DQA-B1 genotypes, thyroid-stimulating hormone (TSH) and free thyroxine (T4). less thanbrgreater than less thanbrgreater thanAt type 1 diabetes diagnosis, 12% of the children had thyroid autoantibodies (60% were girls; p andlt; 0.0001). GADA was positively associated with TPOAb (p andlt; 0.001) and with TGAb (p andlt; 0.001). In addition, ZnT8A was associated with both TPOAb (p = 0.039) and TGAb (p = 0.015). DQB1*05:01 in any genotype was negatively associated with TPOAb (OR 0.55, 95% CI 0.37, 0.83, p value corrected for multiple comparisons (p (c)) = 0.012) and possibly with TGAb (OR 0.55, 95% CI 0.35, 0.87, p (c) = 0.07). Thyroid autoimmunity in children newly diagnosed with type 1 diabetes was rarely (0.45%) associated with onset of clinical thyroid disease based on TSH and free T4. less thanbrgreater than less thanbrgreater thanGADA and ZnT8A increased the risk for thyroid autoimmunity at the time of clinical diagnosis of type 1 diabetes, while HLA-DQB1*05:01 reduced the risk. However, the associations between thyroid autoimmunity and HLA-DQ genotype were weak and did not fully explain the co-occurrence of islet and thyroid autoimmunity.
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- Andersen, Christen L., et al.
(author)
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A phase II study of vorinostat (MK-0683) in patients with polycythaemia vera and essential thrombocythaemia
- 2013
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In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 162:4, s. 498-508
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Journal article (peer-reviewed)abstract
- Inhibition of histone deacetylases may be an important target in patients with myeloproliferative neoplasms. This investigator-initiated, non-randomized, open-label phase II multi-centre study included 63 patients (19 essential thrombocythaemia, 44 polycythaemia vera) from 15 centres. The primary objective was to evaluate if vorinostat was followed by a decline in clonal myeloproliferation as defined by European Leukaemia Net. Thirty patients (48%) completed the intervention period (24 weeks of therapy). An intention-to-treat response rate of 35% was identified. Pruritus was resolved [19% to 0% (P=0.06)] and the prevalence of splenomegaly was lowered from 50% to 27% (P=0.03). Sixty-five per cent of the patients experienced a decrease in JAK2 V617F allele burden (P=0.006). Thirty-three patients (52% of patients) discontinued study drug before end of intervention due to adverse events (28 patients) or lack of response (5 patients). In conclusion, vorinostat showed effectiveness by normalizing elevated leucocyte and platelet counts, resolving pruritus and significantly reducing splenomegaly. However, vorinostat was associated with significant side effects resulting in a high discontinuation rate. A lower dose of vorinostat in combination with conventional and/or novel targeted therapies may be warranted in future studies.
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- Andersen, J. K., et al.
(author)
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Quantification of Greenhouse Gas Emissions from Windrow Composting of Garden Waste
- 2010
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In: Journal of Environmental Quality. - : Wiley. - 0047-2425. ; 39:2, s. 713-724
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Journal article (peer-reviewed)abstract
- Microbial degradation of organic wastes entails the production of various gases such as carbon dioxide (CO2), methane (CH4), nitrous oxide (N2O), and carbon monoxide (CO). Some of these gases are classified as greenhouse gases (GHGs), thus contributing to climate change. A study was performed to evaluate three methods for quantifying GHG emissions from central composting of garden waste. Two small-scale methods were used at a windrow composting facility: a static flux chamber method and a funnel method. Mass balance calculations based on measurements of the C content in the in- and out-going material showed that 91 to 94% of the C could not be accounted for using the small-scale methods, thereby indicating that these methods significantly underestimate GHG emissions. A dynamic plume method (total emission method) employing Fourier Transform Infra Red (FTIR) absorption spectroscopy was found to give a more accurate estimate of the GHG emissions, with CO2 emissions measured to be 127 +/- 15% of the degraded C. Additionally, with this method, 2.7 +/- 0.6% and 0.34 +/- 0.16% of the degraded C was determined to be emitted as CH4 and CO. In this study, the dynamic plume method was a more effective tool for accounting for C losses and, therefore, we believe that the method is Suitable for measuring GHG emissions from composting facilities. The total emissions were found to be 2.4 +/- 0.5 kg CH4-C Mg-1 wet waste (ww) and 0.06 +/- 0.03 kg N2O-N Mg-1 ww from a facility treating 15,540 Mg of garden waste yr(-1), or 111 +/- 30 kg CO2-equivalents Mg-1 ww.
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