Late GU Grade 1 and 2 toxicities were observed in 38% and 48%, respectively, and one patient developed Grade 3 urinary incontinence. Three patients developed urethral stricture (Grade 3), which were corrected with urethral dilatation. The median time to develop Grade 3 complications was

9 months (range, 9–12 months), and the median time for resolution of Grade 3 symptoms was 7 months (range, 23–21 months). No Grade 4 urinary toxicities were observed. Baseline urinary status was found to be significantly associated with post-treatment late urinary toxicity for the development of Common Toxicity Criteria for Adverse Events Grade 2 (p = 0.008) but not for Grade 3 or higher toxicity. Figure 3 illustrates the rates of Grade 2 GU toxicity based on baseline scores. Seventy-eight percent of patients were without significant urinary symptoms (GU Grade 0–1) before the administration of salvage treatment, and 52% of these

remained E7080 nmr free of additional urinary toxicity at the time of last followup. Thus, the majority of urinary toxicity Seliciclib concentration resolved to baseline. Of the three patients who developed Grade 3 urinary toxicity, two were characterized at baseline as having Grade 2 symptoms, and one patient was classified as having Grade 1 symptoms at baseline. The median IPSS at baseline was 6 (range, 1–17), and the median IPSS at last followup was 12 (range, 1–30). Resolution of an elevated IPSS was seen in 41% of patients (returned within 2 points of baseline) within a median time of 4.5 months. IPSS

did not return to baseline values at the time of last followup in 24 patients, with a reported median IPSS value of 14.5 at the time of last followup (range, Thymidylate synthase 5–30). Late Grade 1 and 2 gastrointestinal (GI) toxicities were noted in 43% and 14% of patients, respectively, and 83% of patients were free of Grade 2 or higher GI complications (Fig. 3). GI complications consisted almost entirely of transient rectal bleeding. No Grade 3 or higher GI complications were encountered. The majority of patients were not sexually active at baseline. The median International Index of Erectile Function score before and after treatment was 2 and 1.5, respectively. No dosimetric values such as V100 (volume of the prostate receiving PD) or D90 (dose to 90% of the prostate exposed to PD) were significantly associated with the risk of disease progression or any complications. In this prospective study of salvage HDR monotherapy, 76% of patients were able to achieve biochemical control in a patient population that is by definition radioresistant. Our data suggest that reirradiation with high-dose hypofractionation may be a rational salvage approach to eradicate tumor cells that have survived conventionally fractionated radiotherapy. We also noted an excellent tolerance profile to patients who received salvage HDR despite the high initial doses that patients had received as part of their definitive EBRT.

O procedimento deve ser revisto a cada 3 anos. Nomear um profissional como responsável pelo reprocessamento de material endoscópico, com definição das suas funções e responsabilidades, as quais devem incluir a autonomia para intervir sempre que se identifiquem falhas nas práticas de reprocessamento. Nas UED integradas em unidades de saúde, onde é obrigatória a existência de Comissões de Controlo de Infeção, estas devem participar na definição e monitorização das diretrizes para o reprocessamento. Nas outras UED esta função será atribuída ao Responsável Técnico. Efetuar uma avaliação de riscos anualmente ou sempre

que as circunstâncias se alterem. Promover reuniões regulares de equipa para a análise e discussão das diretrizes e outras questões relacionadas com o reprocessamento. Registar CHIR-99021 clinical trial e analisar os incidentes relacionados com falhas no reprocessamento na UE,

com notificação para o sistema de reporte de eventos adversos da instituição. Registar Trametinib chemical structure evidências de que foram tomadas as medidas apropriadas mediante os incidentes reportados. Realizar auditorias internas aos procedimentos de reprocessamento. Os relatórios das auditorias devem ser analisados e discutidos com o responsável e com a equipa. Os relatórios das auditorias com as propostas de melhoria devem ser enviados ao Conselho de Administração/Responsável Técnico. Disponibilizar as Fichas Técnicas e Fichas de Dados de Segurança dos detergentes, desinfetantes, e do material endoscópico de forma a garantir a sua utilização de acordo com as recomendações do fabricante. Definir um plano de integração para os profissionais que trabalham na área do reprocessamento, com registos comprovativos de formação no manuseamento dos vários tipos de material endoscópico e de reprocessamento existentes na UED. A UED deve disponibilizar uma área separada para o reprocessamento com zonas específicas para sujos, limpos e armazenamento, possibilitando

a circulação G protein-coupled receptor kinase do material endoscópico num só sentido. A área deve dispor de um sistema de ventilação e extração de ar adequado e controlo da temperatura e humidade. Cat IB e IC 1, 5, 6 and 7 Deve existir uma bancada com 2 cubas para lavagem e enxaguamento do material endoscópico. As cubas devem ter o tamanho adequado de modo a permitir a correta lavagem manual do material endoscópico, e a sua localização e disposição devem salvaguardar a exposição dos profissionais de saúde a riscos biológicos, químicos e ergonómicos. Na área de reprocessamento deve existir um lavatório exclusivo para a higienização das mãos8. A área de reprocessamento deve ser concebida de modo a garantir um serviço eficiente e efetivo sem risco para profissionais e utentes. Os profissionais de saúde devem realizar exames de saúde periódicos. Cat 1C O equipamento de proteção individual (EPI) necessário para a atividade de reprocessamento deve estar disponível na UED, em quantidade e qualidade adequadas.

HPLC (SHIMADZU, SPD-10 A VP) with the silicon C18 column was used to separate and analyze PAHs under isocratic condition (solvent – acetonitrile:water (80:20) (v/v) detection wavelength – 254 nm). The flow rate of the mobile phase (acetonitrile) was maintained at 0.5 mL/min. The samples (20 μL) were injected to HPLC analyzer for the analysis of PAHs. Based on the retention time, the fractions were collected and further subjected to analysis. A Hewlett-Packard 689 gas chromatography equipped with

5973 mass spectrometer with HP-5MS (30 m × 0.25 mm I D × 0.25 μm) fused silica capillary column was used for the analysis. The column temperature program was set at 100 °C hold for Selleckchem Nintedanib 1 min, 15 °C/min to 160 °C and 5 °C/min to 300 °C hold for 7 min. The GC injector was held isothermally at 280 °C with a splitless period of 3 min. Helium was used as the carrier gas, at a flow rate of 1 mL/min by using electronic pressure control. The GC–MS Obeticholic Acid chemical structure interface temperature was maintained at 280 °C. The MS was operated in electron impact (EI) ionization mode with electron energy of 70 eV and the scan to determine appropriate masses for selected ion monitoring ranged from 50 to 500 amu (atom to mass unit). Standards from Sigma Aldrich were used for the PAH (anthracene) and their metabolites. GC–MS library search was

used to confirm the metabolites without standards. Genomic DNA (gDNA) of MTCC 5514 was extracted from using DNeasy Blood & Tissue Kit (Qiagen GmbH, Hilden, Germany) following the manufacturer’s protocol for Gram +ve bacteria. The 16S rRNA was PCR amplified using the universal primers 8F: 5′-AGAGTTTGATCCTGGCTCAG-3′ and 1492R: 5′-GGCTACCTTGTTACGACTT-3′ as described by Turner et al. [29]. Homology of the 16S rRNA sequence was compared with sequences available in databases using Blast from the National Center for Biotechnology Information [2] and the Ribosomal Database Project [7]. Alignment of obtained 16S rRNA sequence and sequences from the databases, were all trimmed

to the same length using CLUSTAL Omega algorithm [26]. The sequence details were already submitted to NCBI with the wide accession no. HM145910. The genes encoding the biosurfactant (licA3) and catechol 2,3 dioxygenase (C23O) of the chosen organism was studied Unoprostone and the details were summarized in the following paragraph. The primers for both, surfactant (licA3) and catechol 2,3 dioxygenase (C23O) genes were designed from earlier reports [6] and [27] and were synthesized at Eurofins Genomics India Pvt. Ltd. A portion of surfactant gene 0.26 kb (licA3) gene was pulled out from the genomic DNA using F: 5′- CAA AAG CGC ATC ATA CCA CGT TGA G – 3′ and R: 5′-AGC GGC ACA TAT TGA TGC GGT TC – 3′ primers, with 2.5 U of Taq DNA polymerase in a 25 μL reaction mixture, consisting of 100 ng of genomic DNA, 20 pmol of each primer, 200 μM dNTPs and 1X Taq buffer with 2 mM MgCl2.

Descriptive statistics for the CSQ-13 are presented in Table 2. Table 3 shows the correlation matrix for relations between scores on the CSQ-13 for the five dimensions of cognitive style (internality, globality, stability, self-worth, and negative consequences). As shown in Table 3, scores for all dimensions were positively correlated with one another. The internal reliability of the scores across the five dimensions was good, α = .81. A principal components analysis was performed on the scores for the five dimensions. Kaiser’s (1960) rule, scree-plot analysis, and parallel analysis

using a Monte Carlo analysis with 1000 repetitions, all suggested the extraction of a single factor. This factor (with an eigenvalue of 3.08) accounted for 61.65% of the observed variance. All five dimensions learn more loaded onto this factor, with loadings ranging from .35 to .88. Turning to reliability across the scores for the 13 scenarios, Cronbach’s selleck inhibitor alpha for the CSQ-13 was .91. As a value of alpha greater than .90 suggests that a questionnaire may contain unnecessary duplication of content (Streiner, 2003), the content of the scenarios on the CSQ-13 was re-examined for item redundancy, leading to the removal of two scenarios (‘low average mark for the year’ and ‘low mark in an assignment’) highly similar to another scenario (‘you receive a low mark for an exam’). The final

11 scenarios that remained from the CSQ-13 formed the basis of the second version of the CSQ, the CSQ-11, which was administered via the Internet to a separate sample of participants. The response items for the CSQ-11

were identical to those for the corresponding scenarios in the CSQ-13. Possible scores on the CSQ-11 ranged from 99 to 495. Descriptive statistics for the CSQ-11 are shown in Table 2. Table 4 shows the correlation matrix for relations among scores on the CSQ-11 for the five dimensions of cognitive style (internality, globality, stability, self-worth, and negative consequences). As shown in Table 4, scores for all dimensions were positively correlated with one another. The internal reliability of the scores across the five dimensions was good, α = .86. A principle Fossariinae components analysis was performed on the scores for the five dimensions. Kaiser’s (1960) rule, scree-plot analysis, and parallel analysis using a Monte Carlo analysis with 1000 repetitions, all suggested the extraction of a single factor. This factor (with an eigenvalue of 3.31) accounted for 66.15% of the observed variance. All five dimensions loaded onto this factor, with loadings ranging from .52 to .91. With respect to reliability for scores across the 11 scenarios, Cronbach’s alpha for the CSQ-11 was found to be .89, suggesting that there was still item redundancy (Streiner, 2003).

2 × 10 m3 s− 1 yr− 1.

The negative trend in net precipitation was due to a negative evaporation trend of approximately − 1.6 × 10 m3 s− 1 yr− 1 buy Gefitinib together with a negative precipitation trend of − 3.8 × 10 m3 s− 1 yr− 1. The freshwater discharge into the EMB (i.e. via rivers of the Eastern Basin plus the Black Sea) also displayed a negative trend of –2.4 × 10 m3 s− 1 yr− 1, explained mainly by the building of the Aswan High Dam in 1964 (which reduced the River Nile’s discharge by approximately half) and decreasing net precipitation over the Black Sea Basin (the decrease in Black Sea discharge was estimated to be approximately − 9.8 × 10 m3 s− 1 yr− 1). The negative trends in the freshwater components indicating increasing EMB salinity agree with the findings of Skliris et al. (2007). The EMB monthly mean river runoff ranged from 0.006 × 106 m3 s− 1 in August to 0.018 × 106 m3 s− 1 in April, with an annual average of 0.011 × 106 m3 s− 1. Over the studied 52-year period, Qin – Qout averaged

0.023 ± 0.84 × 106 m3 s− 1, while As(P – E) averaged –0.03 ± 0.04 × 106 m3 s− 1, the difference being balanced by the river discharge ( Table 1). The monthly means of the heat budget components are presented in Table 2 and Figure 14, while the annual means of Fn, Fos and Floss are presented in Figure 15. The heat balance simulations indicate that the heat loss from the open sea was almost balanced by the solar radiation to the open water surface. Heat loss from the open sea ranged from 134.9 W m− 2 to 229.8 W m− 2, while solar radiation to the open water surface ranged from –300.3 W m− 2 in July to –73.3 W m− 2 in December. Cabozantinib price The total heat flux from the EMB surface was negative (indicating fluxes into the water body) from March to August, while it was positive in the rest of the year. Latent heat flux and net long-wave radiation are more important than sensible heat flux in controlling the variability of heat loss from the open sea. The annual average value of Floss was 8.7 W m − 2, which needs to be balanced by the difference in heat transported by the in- and outflowing

water. During the study period, the annual average values of Fn and Fos were 195.6 W m− 2 and − 186.9 W m− 2 respectively. selleck kinase inhibitor Modelled Fn data indicate an increasing trend of 0.07 W m− 2 yr− 1, while Fos data indicate a decreasing trend of approximately 0.07 W m− 2 yr− 1. This indicates an increase in solar radiation into the water body and an increase in net heat loss, probably due to reduced total cloud cover rates. Moreover, the figures indicate a close relationship between the ECMWF meteorological data and the present modelled heat balance components, i.e. Fn, Fos and Floss, with biases of 4, 2.7 and 3.2 W m− 2 respectively. In addition, the positive value of the annual average Floss, 8.7 W m− 2, implies that the EMB imports heat from the Western Basin ( Table 2).

90 J/g and 0.85 J/g, respectively. These authors attributed this enthalpy to gelatinization of starch and suggested that some starch granules retained their crystalline structure after extrusion under these particular extrusion conditions, since the other extrusion conditions did not present δH. Nevertheless, if this was this case, it is not possible to ascertain whether the δH is attributed to gelatinization starch or denaturation protein, ABT-888 in vivo because the starch was not pure (starch-rich fraction) and the temperature of this peak was not reported. Dynamic rheometry was employed to determine the temperature at which storage modulus increases

(TG′inc), and to ascertain storage modulus at the end of heating (G′h) and storage modulus at the end of cooling (G′c). Since the macromolecular substances responsible for network formation in BMS-354825 mouse food systems are primarily polysaccharides and proteins (Tabilo-Munizaga & Barbosa-Cánovas, 2005), the results for dynamic viscoelastic properties were interpreted taking into account the starch and protein content (around 70% and 15%, respectively). The storage and loss moduli analysis of native flours showed that the viscoelastic behavior of these

flours was characteristic of a gel, considering that G′ value was higher than G″ value (Fig. 3A and B). At lower temperatures storage modulus was lower than loss modulus, but at around 60 °C, G′ starts to increase and exceed G″. The temperature at which the storage modulus showed a sharp increase (TG′inc) was considered as the temperature the structure formation started (González et al., 2007). In fact, Carnitine dehydrogenase the native flour TG′inc values were lower (approximately 10 °C) than the Tonset values obtained on DSC analysis at the same concentration (20 g/100g). In fact, there is no consensus on the data obtained from DSC and rheometry techniques (Sandoval et al., 2009). Nevertheless, some authors (Eliasson, 1986 and ∗González et al., 2007b) hold that the initial increase of storage modulus

is related to the hydration and swelling process of the amorphous regions of starch granules, which would be in turn related to the prior development of TG′inc compared to Tonset values. Some reports in the literature state that in the specific case of starchy food products, DSC has not shown sufficient sensitivity to detect the glass transition (Champion, Le Meste, & Simatos, 2000). Based on our results, it seems that the initial swelling process is also not detected by this technique. From the above discussion, it can be concluded that in native flours TG′inc values represent starch gelatinization together with the gelation of protein that presents lower thermal stability (as outlined above). The temperature range in which the storage moduli of native flour reached the maximum values during the heating period was 75–80 °C.

As all cell lines respond to NVP-AUY922, the increase in Hsp70 is very significant and occurs rapidly. In the HCUVA-CC-34 primary culture however, EGFR depletion, ERK1/2 phosphorylation, and Hsp70

up-regulation are not very dramatic, which explain the moderate effects of this drug in anchorage-dependent and anchorage-independent growth assays. Experiments are Doramapimod manufacturer underway to try to identify a possible mechanism of resistance of HCUVA-CC-34 and other colorectal cellular models to NVP-AUY922. Since all our cellular models, apart from the exception just mentioned, were sensitive to NVP-AUY922, we sought to find markers of sensitivity/resistance to 17-AAG. In fact, phospho-kinase arrays were performed in 17-AAG–sensitive as well as in 17-AAG–resistant cell lines with the intention to find putative markers. However, we could not clearly associate differences found between cell lines to resistance to this drug. As it has been suggested that ABC transporters may play a role in resistance to Hsp90 inhibitors, we analyzed Mdr-1, MRP1, and BRCP1 protein levels

in these cell lines and found that none of the 17-AAG–resistant pancreatic and colorectal carcinoma cell lines expressed these transporters, find more with the exception of Caco-2 cells that express very low levels of BRCP1. However, many of the 17-AAG–sensitive cell lines express some of these ABC transporters (Figure 7). Therefore, we can rule out the role of these ABC transporters

in 17-AAG resistance. In addition to Pgp (Mdr-1), it has been suggested in several reports that NQO1/DT-diaphorase is necessary for benzoquinone ansamycin function. This enzyme is able to metabolize quinones to the corresponding hydroquinones, which are more stable and bind Hsp90 with greater affinity. We have found that the 17-AAG–resistant pancreatic carcinoma PANC-1 and CFPAC-1 cells lack NQO1 protein and activity (Figure 8), confirming the results previously reported by Siegel et al. [39]. The 17-AAG–resistant Caco-2 cells also lack NQO1 protein and enzymatic activity. However, LoVo cells, which are also devoid of NQO1 enzyme (Figure 8), are still responsive to 17-AAG, as demonstrated especially in soft Sclareol agar assays and cell cycle analyses (Figure 2 and Figure 3). We speculate that other reductases, albeit with less potency, may be able to reduce 17-AAG to 17-AAGH2 in these cells. Another possibility is that although less potent, the nonreduced benzoquinones may also have an activity and be able to exert the same effects as their reduced counterparts at higher concentrations. When we blocked NQO1 activity in 17-AAG–sensitive cell lines with ES936, these cells were still growth inhibited by 17-AAG (Figure 9).

arabidopsis.org/), and the UniProt Knowledgebase (http://www.ebi.ac.uk/).

Functional annotations were then assigned based on OSI-744 in vivo sequence similarity (with E-value of 10− 5) with manual adjustment when necessary. All of the probes were grouped into functional categories and metabolic pathways based on the Mips Functional Catalogue (http://mips.gsf.de/) and KEGG [51], [52] and [53]. Adhering to the established method [54] and [55], we identified statistically enriched KEGG pathways and gene families of transcription factors in differentially expressed genes based on a background distribution from the whole chip. The expression levels of genes were measured by detection calls and signal intensities using Micro Array Suite 5.0 software with a target signal of 100. All pair-wise differentially expressed genes were identified using SAM software (http://www-stat.stanford.edu/~tibs/SAM/) to analyze data from all remaining maize probe sets. A false discovery rate parameter of 1% was set for the SAM analysis. Genes that were called absent more than twice among the three replicates in both the control and treatment arrays were then considered to be not unexpressed under both conditions and were excluded from the list. A 5 μg sample of total RNA was used for cDNA synthesis using the Invitrogen Reverse Transcription Reagents

Kit (Invitrogen). Gene-specific primers were designed using Primer Express 2.0 software (Applied Biosystems) and synthesized by Sangon Biotech Co. Ltd. (Shanghai). Relative quantitative analysis was performed using an Applied Biosystems 7900HT real-time PCR system (Applied Biosystems) under the Proteases inhibitor following conditions: 94 °C for 3 min (1 cycle); 94 °C for 30 s, 60 °C for 30 s, and 72 °C for 30 s (40 cycles). Transcript abundance was identified using SYBR

Green PCR Master Mix (Applied Biosystems). Each reaction contained 1 × buffer, 0.25 μmol L− 1 of each primer, and approximately 2 ng of cDNA in a final volume of 20 μL. Three replicates were employed for each tested sample and template-free negative control. Mitochondrial 5S RNA was used as an internal control to normalize all data. Melting curves were performed on the product to test whether only a single product was amplified without primer-dimers and other bands. The resultant products with Arachidonate 15-lipoxygenase all primer combinations were initially visualized on 2% agarose gels to confirm the generation of a single product of the correct size. To identify miRNAs in developing kernel of a maize viviparous mutant at different developmental stages, RNAs of 18 to 26 nt in length were purified and cloned from small RNAs (~ 200 nt) isolated from germinating maize kernels for subsequent sequence analysis. Approximately 64 concatamer clones were sequenced to generate 540 sequences after discarding low-quality and self-ligated linker sequences. Of these, 56 small RNA-cDNA sequences were outside the expected range of nucleotide lengths (18–26 nt).

The ratios of nitrogen to phosphorus are the key fraction Doramapimod of the Redfield ratio. PC1 represented nutrient limitation to phytoplankton growth in the study area. PC2, explaining 18.80% of the total variance, had positive loadings on DP, and negative loadings on DO and Chl a, which illustrated the similar features of the original data that DO and Chl a are high in coastal shallow stations and low in deep stations offshore ( Figures 2f–g). PC3, explaining 12.97% of the total variance, had positive loadings on PO4-P and negative loadings on pH. pH is determined mainly by biological activities,

and PO4-P comes mainly from the upwelling areas and the estuary in the northern SCS. PC3 therefore represented the impact of macronutrients on biological activities in the upwelling areas and the estuary. PC4, explaining

PARP activation 11.44% of the total variance, had negative loadings on SiO3-Si. SiO3-Si is replenished mainly by the upwelling from the deep sea in the northern SCS ( Chen et al. 2001). PC4 represented the features of upwelling. PC5, explaining 7.81% of the total variance, had strong positive loadings on NH4-N and represented the anthropogenic pollution near the Pearl River Estuary. The massive economic growth and urban development in the Pearl River Delta have resulted in excessive discharges of wastewater in the Pearl River Estuary. NH4-N is an important indicator of anthropogenic pollution in the Pearl River Estuary. Figure 4 shows the horizontal distribution

patterns of silicate at different depths, including the surface, 50 m , 75 m , 100 m , 150 m  and 200 m . At the surface, the concentration of silicate is low (< 3 μmol dm−3) in most of the northern SCS ( Figure 4a). Three high concentration zones can be clearly distinguished: (1) the Taiwan Shoals upwelling in the north-east of the PIS showed a high concentration of ~ 16.46 μmol dm−3; (2) the northern perennial cold cyclonic eddy in the south-west of the PIS had a relatively lower concentration of ~ 5.29 μmol Sclareol dm−3 at the centre; (3) the upwelling region in the west of the PIS was ~ 11.96 μmol dm−3 ( Figure 4a). The spatial distribution of silicate clearly shows three upwelling regions. In Figures 4a–f, the Taiwan Shoals upwelling has been formed at 200 m  depth and is moving to the north-east, and its central concentration of silicate is decreasing from 65.3 μmol dm−3 to 16.46 μmol dm−3. These results illustrate that the Taiwan Shoals upwelling is formed by the deep-sea current climbing up the continental shelf near the PIS in a north-easterly direction. The northern part of the perennial cold cyclonic eddy is steady and stays at the same position in every layer, which is formed by the vertical uplifting current. The upwelling in the west of the PIS is detected at 100 m  depth, and the horizontal distribution traces its process of formation. The upwelling in TSLS ( Han 1998, Shen & Shi 2006) and in the perennial cold cyclonic eddy ( Wu 1991, Huang et al.

” (Project Manager D). ICT systems were sometimes visible in projects, in cases where they were used to improve communication with patients (e.g., through websites or providing patients with access to medical records) and to enable patients to track their behavior, health values, and progress. In summary, although practices used different strategies, our interviews with project managers confirmed that the projects used the DMPs to “offer more.” They changed the nature of conversations with patients in individual and group settings, and improved patient

tracking through ICT systems. They also ventured beyond the medical practice into the community to address health behavior changes more comprehensively. Overall, KU-60019 mouse both the quantitative and qualitative click here results showed that DMP implementation improved patients’ health behavior. These findings are in line with those of Hung and colleagues [33], who found that interventions

such as DMPs based on the CCM offer a useful framework for preventive purposes by addressing important risky health behaviors. The percentages of patient participants meeting the Dutch standard for healthy physical activity (63.7% in 2010, 68.5% in 2011) were higher than the average percentages in the general adult (18+ years) Dutch population (58.1% in 2010, 58.0% in 2011), and reflect a substantial improvement not seen in the general population [34]. The proportion of current smokers (25.0% in 2010 vs. 17.8% in 2011; 7.2% reduction) among chronically Evodiamine ill patients also decreased substantially. The mean prevalence of smoking in the general Dutch population was 25.6% in 2010 and 2011 [35]. There is evidence from large long-term randomized controlled trials that quality of life of chronically ill patients slowly deteriorates over time, especially in the placebo

groups but sometimes also in the intervention groups [36] and [37]. Although physical quality of life also deteriorated among patients in our study, we expect that improvements in health behavior (physical activity and smoking) will prevent or slow down the deterioration of physical quality of life normally seen in a chronic illness population. Qualitative research indicated many of the aspects of DMPs targeted at improving health behavior are expected to have a longer-term impact on quality of life. In a meta-analysis of interventions based on the CCM to improve care for chronic illnesses Tsai and colleagues [23] found that the evidence on quality of life outcomes was mixed. Condition-specific quality of life scales are known to be more sensitive to changes in clinical status compared to generic measures of quality of life such as the SF-36. However, we have chosen the latter, because the generic quality of life measures can be used in a wide variety of diseases, as was the case in our project.