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This article focuses on the interdependence between the state and Sweden’s largest non-governmental victim support umbrella organization, Victim Support Sweden (VSS). In particular, it examines how government funding of VSS has developed since the end of the 1980s. Based on a qualitative analysis of government bills and VSS’s annual reports, the article gives a detailed account of how a non-governmental organization and the state are interconnected in a complementary relationship. The results show that VSS has differentiated itself from the state and government agencies by defining its victim support volunteers as ‘fellow human beings’. The state and VSS have, however, always been interdependent, which blurs the line between the two. VSS has relied on government grants, while the state has leaned on VSS for victim support. In addition, many of VSS’s local victim support centers have signed cooperation agreements with municipalities, which may give municipalities greater control over the centers’ work.

Francisella tularensis is a bacterial pathogen that causes the zoonotic disease tularemia and is important to biodefense. Currently, the only vaccine known to confer protection against tularemia is a specific live vaccine strain (designated LVS) derived from a virulent isolate of Francisella tularensis subsp. holarctica. The origin and source of attenuation of this strain are not known. To assist with the design of a defined live vaccine strain, we sought to determine the genetic basis of the attenuation of LVS. This analysis relied primarily on the comparison between the genome of LVS and Francisella tularensis holarctica strain FSC200, which differ by only 0.08% of their nucleotide sequences. Under the assumption that the attenuation was due to a loss of function(s), only coding regions were examined in this comparison. To complement this analysis, the coding regions of two slightly more distantly related Francisella tularensis strains were also compared against the LVS coding regions. Thirty-five genes show unique sequence variations predicted to alter the protein sequence in LVS compared to the other Francisella tularensis strains. Due to these polymorphisms, the functions of 15 of these genes are very likely lost or impaired. Seven of these genes were demonstrated to be under stronger selective constraints, suggesting that they are the most probable to be the source of LVS attenuation and useful for a newly defined vaccine.

ABSTRACTFrancisella tularensisis a bacterial pathogen that causes the zoonotic disease tularemia and is important to biodefense. Currently, the only vaccine known to confer protection against tularemia is a specific live vaccine strain (designated LVS) derived from a virulent isolate of Francisella tularensissubsp. holarctica. The origin and source of attenuation of this strain are not known. To assist with the design of a defined live vaccine strain, we sought to determine the genetic basis of the attenuation of LVS. This analysis relied primarily on the comparison between the genome of LVS and Francisella tularensis holarcticastrain FSC200, which differ by only 0.08% of their nucleotide sequences. Under the assumption that the attenuation was due to a loss of function(s), only coding regions were examined in this comparison. To complement this analysis, the coding regions of two slightly more distantly related Francisella tularensisstrains were also compared against the LVS coding regions. Thirty-five genes show unique sequence variations predicted to alter the protein sequence in LVS compared to the other Francisella tularensisstrains. Due to these polymorphisms, the functions of 15 of these genes are very likely lost or impaired. Seven of these genes were demonstrated to be under stronger selective constraints, suggesting that they are the most probable to be the source of LVS attenuation and useful for a newly defined vaccine.

ABSTRACTFrancisella tularensissubsp. tularensis(type A) strain SCHU S4 is a prototypic strain of the pathogen that is highly virulent for humans and other mammals. Its intradermal (i.d.) 50% lethal dose (LD50) for mice is <10 CFU. We discovered a spontaneous mutant, designated FSC043, of SCHU S4 with an i.d. LD50of >108CFU. FSC043 effectively vaccinated mice against challenge with a highly virulent type A strain, and the protective efficacy was at least as good as that of F. tularensisLVS, an empirically attenuated strain which has been used as an efficacious human vaccine. Comparative proteomics was used to identify two proteins of unknown function that were identified as defective in LVS and FSC043, and deletion mutants of SCHU S4 were created for each of the two encoding genes. One mutant, the ΔFTT0918 strain, failed to express a 58-kDa protein, had an i.d. LD50of ∼105CFU, and was found to be less capable than SCHU S4 of growing in peritoneal mouse macrophages. Mice that recovered from sublethal infection with the ΔFTT0918 mutant survived when challenged 2 months later with >100 LD50s of the highly virulent type A strain FSC033. This is the first report of the generation of defined mutants of F. tularensissubsp. tularensisand their use as live vaccines.

Francisella tularensis subsp. tularensis (type A) strain SCHU S4 is a prototypic strain of the pathogen that is highly virulent for humans and other mammals. Its intradermal (i.d.) 50% lethal dose (LD50) for mice is <10 CFU. We discovered a spontaneous mutant, designated FSC043, of SCHU S4 with an i.d. LD50 of >108 CFU. FSC043 effectively vaccinated mice against challenge with a highly virulent type A strain, and the protective efficacy was at least as good as that of F. tularensis LVS, an empirically attenuated strain which has been used as an efficacious human vaccine. Comparative proteomics was used to identify two proteins of unknown function that were identified as defective in LVS and FSC043, and deletion mutants of SCHU S4 were created for each of the two encoding genes. One mutant, the ΔFTT0918 strain, failed to express a 58-kDa protein, had an i.d. LD50 of ∼105 CFU, and was found to be less capable than SCHU S4 of growing in peritoneal mouse macrophages. Mice that recovered from sublethal infection with the ΔFTT0918 mutant survived when challenged 2 months later with >100 LD50s of the highly virulent type A strain FSC033. This is the first report of the generation of defined mutants of F. tularensis subsp. tularensis and their use as live vaccines.

p58/ERGIC-53 is an animal calcium-dependent lectin that cycles between the endoplasmic reticulum (ER) and the Golgi complex and appears to act as a cargo receptor for a subset of soluble glycoproteins exported from the ER. We have determined the crystal structure of the carbohydrate recognition domain (CRD) of p58, the rat homologue of human ERGIC-53, to 1.46 Å resolution. The fold and ligand binding site are most similar to those of leguminous lectins. The structure also resembles that of the CRD of the ER folding chaperone calnexin and the neurexins, a family of non-lectin proteins expressed on neurons. The CRD comprises one concave and one convex β-sheet packed into a β-sandwich. The ligand binding site resides in a negatively charged cleft formed by conserved residues. A large surface patch of conserved residues with a putative role in protein-protein interactions and oligomerization lies on the opposite side of the ligand binding site. Together with previous functional data, the structure defines a new and expanding class of calcium-dependent animal lectins and provides a starting point for the understanding of glycoprotein sorting between the ER and the Golgi.

Caring practices are expected to rely on scientific knowledge, thus results from research must be known to practitioners. The aim of this study was to explore nurses' view of their opportunities to update nursing research and to see if differences emerged between long-term and acute care settings. Data were collected through a semi-structured questionnaire from 43 registered nurses on duty during one day-shift and one night-shift in two nursing homes and on two medical wards in an acute care hospital. The results showed that all nurses held very positive opinions on the usefulness of nursing research for their practice. A major concern reported by both the nursing home nurses and the medical ward nurses was the lack of support and interest from their superiors. Hindrances to up-date research were the poor supply of scientific nursing journals, lack of time and opportunities for discussion with nursing colleagues and lack of own knowledge of relevant information channels. Nursing students were the main informants of research articles. Conclusions made were that all nurses recognized the professional importance of nursing research but lacked up-dated knowledge and administrative support. In this samle no differences of specific importence could be noted between the organizational settings. It is suggested that support for and barriers to nursing research information is the criterion for quality assessment of care institutions.

In a separate lipid intervention clinic integrated within the framework of a multiphasic preventive medical population program in Malmö, 401 of 2431 screening attenders in a male birth-year cohort born in 1927 and 1928 had elevated values of triglyceride and/or cholesterol. Hypertriglyceridemia was more than three times as frequent as hypercholesterolemia. Of these attenders 20% had normal values at the second control, 5% did not attend the second test and 92 (31.2%) of the remaining were referred to other clinics because of other high risk factors. Thus, 209 (8.6% of the screening attenders) males born in 1927 and 1928 attended the lipid clinic for isolated hyperlipidemia. Disregarding a 5-year drop-out frequency of 13§, a significant reduction in the lipids was obtained during the follow-up period in those remaining in treatment. This study demonstrates the feasibility in taking care of hyperlipidemic individuals after a screening detection program. Detection and treatment of hyperlipidemia should of course also be initiated in the individual case in ordinary medical practice.

We have used a 58 kDa membrane protein (p58) as a marker to study the transport pathway between the rough endoplasmic reticulum (ER) and the Golgi apparatus. Immunolocalization of p58 in fibroblasts showed its presence in a single cisterna and in small tubular and vesicular elements at the cis side of the Golgi apparatus. In addition, the protein was detected in large (200–500 nm in diameter) tubulovesicular structures, clustered in the Golgi region but also found in peripheral locations. These represent intermediates in ER to Golgi transport since they contained newly synthesized viral glycoproteins, arrested in cells at I5°C. The peripheral structures accumulated at low temperature but reclustered rapidly to the Golgi region upon shift of cells back to 37°C. This movement involved long intracellular distances and was efficiently inhibited by nocodazole, indicating that it requires the integrity of microtubules. In contrast, reclustering was unaffected by brefeldin A (BFA), suggesting that this compound affects ER to Golgi transport prior to the temperature-sensitive step. In BFA-treated cells p58 was localized to scattered, tubular, smooth ER clusters, found in close association with rough ER cisternae. The cellular distribution of the intermediate elements indicates that the sites of protein exit are widely distributed within the rough ER network. We suggest that the smooth ER locations where p58 accumulates in BFA-treated cells could represent such peripheral exit sites.

Background Francisella tularensis subspecies tularensis and holarctica are pathogenic to humans, whereas the two other subspecies, novicida and mediasiatica, rarely cause disease. To uncover the factors that allow subspecies tularensis and holarctica to be pathogenic to humans, we compared their genome sequences with the genome sequence of Francisella tularensis subspecies novicida U112, which is nonpathogenic to humans.Results Comparison of the genomes of human pathogenic Francisella strains with the genome of U112 identifies genes specific to the human pathogenic strains and reveals pseudogenes that previously were unidentified. In addition, this analysis provides a coarse chronology of the evolutionary events that took place during the emergence of the human pathogenic strains. Genomic rearrangements at the level of insertion sequences (IS elements), point mutations, and small indels took place in the human pathogenic strains during and after differentiation from the nonpathogenic strain, resulting in gene inactivation.Conclusion The chronology of events suggests a substantial role for genetic drift in the formation of pseudogenes in Francisella genomes. Mutations that occurred early in the evolution, however, might have been fixed in the population either because of evolutionary bottlenecks or because they were pathoadaptive (beneficial in the context of infection). Because the structure of Francisella genomes is similar to that of the genomes of other emerging or highly pathogenic bacteria, this evolutionary scenario may be shared by pathogens from other species.

To study the effects of the new vasodilating blocking agent carvedilol on a variety of metabolic, hemodynamic, and ECG parameters of importance for the clinical outcome of acute myocardial infarction AMI, we infused epinephrine EPI in healthy male volunteers on two separate occasions to serum concentrations of the same level reached in AMI. Before the EPI infusions, the volunteers were pretreated for 2 weeks with either carvedilol or placebo in randomized order. EPI caused significant decreases in serum levels Spotassium 0.62 mM, Smagnesium 0.07 mM, Scalcium 0.12 mM, and Sphosphate 0.26 mM. After pretreatment with carvedilol, the decreases in Scalcium and Sphosphate were partly prevented and those in Spotassium and Smagnesium were completely inhibited. Shortterm treatment with carvedilol significantly decreased Sinsulin and serum Cpeptide and significantly attenuated the EPIinduced increase in Bglucose observed after placebo. The EPI infusion significantly increased serum concentrations of free fatty acids and glycerol. These increases were significantly attenuated by carvedilol, whereas carvedilol had no significant affects of a variety of other lipid variables. EPI infusion caused a significant p < 0.01 increase in systolic blood pressure SBP from 124.8 ± 8.1 to 135.8 ± 12.5 mm Hg and an increase in heart rate HR from 71.0 ± 11.5 to 77.2 ± 12.2, resulting in a significant increase in ratepressure product RPP. This estimate of cardiac work was significantly p < 0.05 reduced by pretreatment with carvedilol. A significant p < 0.01 increase in QTcduration from 0.41 ± 0.02 s to 0.44 ± 0.03 s was evident during the EPI infusion after pretreatment with placebo. This increase was completely prevented by carvedilol. Pretreatment with carvedilol apparently prevented or attenuated many of the effects of EPI, which in the clinical setting of AMI may have a deleterious impact on clinical outcome.