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1.  Life values as predictors of pain, disability and sick leave among Swedish registered nurses: a longitudinal study 
BMC Nursing  2011;10:17.
Background
Prospective studies on high-risk populations, such as subgroups of health care staff, are limited, especially prospective studies among staff not on sick-leave. This paper is a report of a longitudinal study conducted to describe and compare the importance and consistency of life domains among registered nurses (RNs) working in a Swedish hospital and evaluate a model based on the consistency of valued life domains for prediction of pain, disability and sick leave.
Method
Importance and consistency ratings of life values, in 9 domains, were collected during 2003 and 2006 from 196 RNs using the Valued Living Questionnaire (VLQ). Logistic regression analyses were used for prediction of pain, disability and sick leave at the three-year follow-up. The predictors family relations, marriage couples/intimate relations, parenting, friends/social life, work, education, leisure time, psychological well-being, and physical self-care were used at baseline.
Results
RNs rated life values regarding parenting as most important and with the highest consistency both at baseline and at follow-up. No significant differences were found between RNs' ratings of importance and consistency over the three-year period, except for friends/social relations that revealed a significant decrease in importance at follow-up. The explanatory models for pain, disability and sick leave significantly predicted pain and disability at follow-up. The odds of having pain were significantly increased by one consistency rating (psychological well-being), while the odds were significantly decreased by physical self-care. In the model predicting disability, consistency in psychological well-being and education significantly increased the odds of being disabled, while consistency in physical self-care significantly decreased the odds.
Conclusion
The results suggest that there might be a link between intra-individual factors reflecting different aspects of appraised life values and musculoskeletal pain (MSP).
doi:10.1186/1472-6955-10-17
PMCID: PMC3198938  PMID: 21958331
2.  Polymorphic Mutation Frequencies in Escherichia coli: Emergence of Weak Mutators in Clinical Isolates 
Journal of Bacteriology  2004;186(16):5538-5542.
Polymorphisms in the rifampin resistance mutation frequency (f) were studied in 696 Escherichia coli strains from Spain, Sweden, and Denmark. Of the 696 strains, 23% were weakly hypermutable (4 × 10−8 ≤ f < 4 × 10−7), and 0.7% were strongly hypermutable (f ≥ 4 × 10−7). Weak mutators were apparently more frequent in southern Europe and in blood isolates (38%) than in urinary tract isolates (25%) and feces of healthy volunteers (11%).
doi:10.1128/JB.186.16.5538-5542.2004
PMCID: PMC490890  PMID: 15292159
3.  Biological Costs and Mechanisms of Fosfomycin Resistance in Escherichia coli 
Fosfomycin is a cell wall inhibitor used mainly for the treatment of uncomplicated lower urinary tract infections. As shown here, resistance to fosfomycin develops rapidly in Escherichia coli under experimental conditions, but in spite of the relatively high mutation rate in vitro, resistance in clinical isolates is rare. To examine this apparent contradiction, we mathematically modeled the probability of resistance development in the bladder during treatment. The modeling showed that during a typical episode of urinary tract infection, the probability of resistance development was high (>10−2). However, if resistance was associated with a reduction in growth rate, the probability of resistance development rapidly decreased. To examine if fosfomycin resistance causes a reduced growth rate, we isolated in vitro and in vivo a set of resistant strains. We determined their resistance mechanisms and examined the effect of the different resistance mutations on bacterial growth in the absence and presence of fosfomycin. The types of mutations found in vitro and in vivo were partly different. Resistance in the mutants isolated in vitro was caused by ptsI, cyaA, glpT, uhpA/T, and unknown mutations, whereas no cyaA or ptsI mutants could be found in vivo. All mutations caused a decreased growth rate both in laboratory medium and in urine, irrespective of the absence or presence of fosfomycin. According to the mathematical model, the reduced growth rate of the resistant strains will prevent them from establishing in the bladder, which could explain why fosfomycin resistance remains rare in clinical isolates.
doi:10.1128/AAC.47.9.2850-2858.2003
PMCID: PMC182645  PMID: 12936984
4.  Carbon Starvation Can Induce Energy Deprivation and Loss of Fermentative Capacity in Saccharomyces cerevisiae 
Seven different strains of Saccharomyces cerevisiae were tested for the ability to maintain their fermentative capacity during 24 h of carbon or nitrogen starvation. Starvation was imposed by transferring cells, exponentially growing in anaerobic batch cultures, to a defined growth medium lacking either a carbon or a nitrogen source. After 24 h of starvation, fermentative capacity was determined by addition of glucose and measurement of the resulting ethanol production rate. The results showed that 24 h of nitrogen starvation reduced the fermentative capacity by 70 to 95%, depending on the strain. Carbon starvation, on the other hand, provoked an almost complete loss of fermentative capacity in all of the strains tested. The absence of ethanol production following carbon starvation occurred even though the cells possessed a substantial glucose transport capacity. In fact, similar uptake capacities were recorded irrespective of whether the cells had been subjected to carbon or nitrogen starvation. Instead, the loss of fermentative capacity observed in carbon-starved cells was almost surely a result of energy deprivation. Carbon starvation drastically reduced the ATP content of the cells to values well below 0.1 μmol/g, while nitrogen-starved cells still contained approximately 6 μmol/g after 24 h of treatment. Addition of a small amount of glucose (0.1 g/liter at a cell density of 1.0 g/liter) at the initiation of starvation or use of stationary-phase instead of log-phase cells enabled the cells to preserve their fermentative capacity also during carbon starvation. The prerequisites for successful adaptation to starvation conditions are probably gradual nutrient depletion and access to energy during the adaptation period.
doi:10.1128/AEM.69.6.3251-3257.2003
PMCID: PMC161471  PMID: 12788723
5.  Error-prone initiation factor 2 mutations reduce the fitness cost of antibiotic resistance 
Molecular Microbiology  2010;75(5):1299-1313.
Mutations in the fmt gene (encoding formyl methionine transferase) that eliminate formylation of initiator tRNA (Met-tRNAi) confer resistance to the novel antibiotic class of peptide deformylase inhibitors (PDFIs) while concomitantly reducing bacterial fitness. Here we show in Salmonella typhimurium that novel mutations in initiation factor 2 (IF2) located outside the initiator tRNA binding domain can partly restore fitness of fmt mutants without loss of antibiotic resistance. Analysis of initiation of protein synthesis in vitro showed that with non-formylated Met-tRNAi IF2 mutants initiated much faster than wild-type IF2, whereas with formylated fMet-tRNAi the initiation rates were similar. Moreover, the increase in initiation rates with Met-tRNAi conferred by IF2 mutations in vitro correlated well with the increase in growth rate conferred by the same mutations in vivo, suggesting that the mutations in IF2 compensate formylation deficiency by increasing the rate of in vivo initiation with Met-tRNAi. IF2 mutants had also a high propensity for erroneous initiation with elongator tRNAs in vitro, which could account for their reduced fitness in vivo in a formylation-proficient strain. More generally, our results suggest that bacterial protein synthesis is mRNA-limited and that compensatory mutations in IF2 could increase the persistence of PDFI-resistant bacteria in clinical settings.
doi:10.1111/j.1365-2958.2010.07057.x
PMCID: PMC2859245  PMID: 20132454
6.  The Study of Active Monitoring in Sweden (SAMS): A randomized study comparing two different follow-up schedules for active surveillance of low-risk prostate cancer 
Scandinavian Journal of Urology  2013;47(5):347-355.
Objective
Only a minority of patients with low-risk prostate cancer needs treatment, but the methods for optimal selection of patients for treatment are not established. This article describes the Study of Active Monitoring in Sweden (SAMS), which aims to improve those methods.
Material and methods
SAMS is a prospective, multicentre study of active surveillance for low-risk prostate cancer. It consists of a randomized part comparing standard rebiopsy and follow-up with an extensive initial rebiopsy coupled with less intensive follow-up and no further scheduled biopsies (SAMS-FU), as well as an observational part (SAMS-ObsQoL). Quality of life is assessed with questionnaires and compared with patients receiving primary curative treatment. SAMS-FU is planned to randomize 500 patients and SAMS-ObsQoL to include at least 500 patients during 5 years. The primary endpoint is conversion to active treatment. The secondary endpoints include symptoms, distant metastases and mortality. All patients will be followed for 10–15 years.
Results
Inclusion started in October 2011. In March 2013, 148 patients were included at 13 Swedish urological centres.
Conclusions
It is hoped that the results of SAMS will contribute to fewer patients with indolent, low-risk prostate cancer receiving unnecessary treatment and more patients on active surveillance who need treatment receiving it when the disease is still curable. The less intensive investigational follow-up in the SAMS-FU trial would reduce the healthcare resources allocated to this large group of patients if it replaced the present standard schedule.
doi:10.3109/21681805.2013.813962
PMCID: PMC3810035  PMID: 23883427
biopsy; patient selection; prostatic neoplasm; randomized clinical trial; watchful waiting.

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