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- Franzen, Oscar, et al.
(author)
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Draft genome sequencing of Giardia intestinalis assemblage B isolate GS : is human giardiasis caused by two different species?
- 2009
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In: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 5:8, s. e1000560-
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Journal article (peer-reviewed)abstract
- Giardia intestinalis is a major cause of diarrheal disease worldwide and two major Giardia genotypes, assemblages A and B, infect humans. The genome of assemblage A parasite WB was recently sequenced, and the structurally compact 11.7 Mbp genome contains simplified basic cellular machineries and metabolism. We here performed 454 sequencing to 16 x coverage of the assemblage B isolate GS, the only Giardia isolate successfully used to experimentally infect animals and humans. The two genomes show 77% nucleotide and 78% amino-acid identity in protein coding regions. Comparative analysis identified 28 unique GS and 3 unique WB protein coding genes, and the variable surface protein (VSP) repertoires of the two isolates are completely different. The promoters of several enzymes involved in the synthesis of the cyst-wall lack binding sites for encystation-specific transcription factors in GS. Several synteny-breaks were detected and verified. The tetraploid GS genome shows higher levels of overall allelic sequence polymorphism (0.5 versus <0.01% in WB). The genomic differences between WB and GS may explain some of the observed biological and clinical differences between the two isolates, and it suggests that assemblage A and B Giardia can be two different species.
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- Nilsson, S., et al.
(author)
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Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study
- 2007
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In: Lancet Oncol. - 1470-2045 .- 1474-5488. ; 8:7, s. 587-594
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Journal article (peer-reviewed)abstract
- BACKGROUND: The alpha-emitter radium-223 ((223)Ra) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer. We aimed to study mature outcomes from a randomised, multicentre, phase II study of (223)Ra. METHODS: Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of (223)Ra (50 kBq/kg, 33 patients) or placebo (31 patients), given every 4 weeks. Primary endpoints were change in bone-alkaline phosphatase (ALP) concentration and time to skeletal-related events (SREs). Secondary endpoints included toxic effects, time to prostate-specific-antigen (PSA) progression, and overall survival. All tests were done at a 5% significance level, based on intention to treat. FINDINGS: Median relative change in bone-ALP during treatment was -65.6% (95% CI -69.5 to -57.7) and 9.3% (3.8-60.9) in the (223)Ra group and placebo groups, respectively (p<0.0001, Wilcoxon ranked-sums test). Hazard ratio for time to first SRE, adjusted for baseline covariates, was 1.75 (0.96-3.19, p=0.065, Cox regression). Haematological toxic effects did not differ significantly between two groups. No patient discontinued (223)Ra because of treatment toxicity. Median time to PSA progression was 26 weeks (16-39) versus 8 weeks (4-12; p=0.048) for (223)Ra versus placebo, respectively. Median overall survival was 65.3 weeks (48.7-infinity) for (223)Ra and 46.4 weeks (32.1-77.4) for placebo (p=0.066, log rank). The hazard ratio for overall survival, adjusted for baseline covariates was 2.12 (1.13-3.98, p=0.020, Cox regression). INTERPRETATION: (223)Ra was well tolerated with minimum myelotoxicity, and had a significant effect on bone-ALP concentrations. Larger clinical trials are warranted to study (223)Ra on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer. Bone-targeting properties of (223)Ra could also potentially be used for treating skeletal metastasis from other primary cancers.
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- Urban, Susanne, 1966-
(author)
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Att ordna staden : Den nya storstadspolitiken växer fram
- 2005
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Doctoral thesis (other academic/artistic)abstract
- The sociology of the city has two faces: one of threat and one of promises. Originally, the city was portrayed as a threat to social life and individual identity, while, in contrast, the neighbourhood was seen to include the promise of restoring basic social relations to the web of city life. Later, the neighbourhood itself came to be perceived as a threat, as it was seen to separate people from one another. The solution to this dilemma was that the neighbourhood should be an arena for meetings between different groups, supplying not strong ‘excluding’ bonds, but subtle ‘bridge-building’ ones.The aim of the first part in the thesis is to study the public view of the neighbourhood and its significance for social integration. The aim of the second part is to investigate the new metropolitan policy approach to attain the challenging goal of integration at the local municipal level. This is explored using the theoretical model of a democratic welfare society, as developed by Jürgen Habermas.Ethnic housing segregation, as a social problem, has evolved in several stages. In 1990 the promise became to combat ”problem areas” through various methods for integration, commitment, improved reputation, an increasing sense of community and environmental improvement. More recently, since 2000, the question of ethnic housing segregation appears to be being dealt with through a process of delegation of responsibility to various authorities with different areas of expertise and to local municipal authorities. This suggests a possible fragmentalization of approaches to ethnic housing segregation. In official discussion of ethnic housing segregation, an acknowledgement of the relational approach has been severely lacking. A review of the literature of neighbourhood effects shows that ethnic clustering can result in positive as well in negative effects. In a relational perspective, local networks are one of several other relations that, in combination with different structures and power distributions, effects integration between ethnic groups in the society.Principles from new metropolitan policy, referred to as ”bottom-up”, are similar to Habermas’ ideal. However, the concrete experiences highlight the difficulty in offering possibilities for rational communication, development of communicative knowledge, and even less communicative power. The new metropolitan policy has posed a new formulation of threat and promise. The dichotomy of segregation versus integration has developed into one of exclusion versus participation. The ideal has changed from formal to subjective integration, which includes civil participation in state business. The neighbourhood has served as one arena to start inclusive processes. The practice, on the contrary, is still dominated by measures aimed at making society work more efficiently through state intrusion into private matters i.e. governmentalization.
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