Long‐term effects of angiotensin II blockade with irbesartan on inflammatory markers in hemodialysis patients: A randomized double blind placebo controlled trial (SAFIR study)

Introduction: Low‐grade chronic inflammation is common in hemodialysis (HD) patients. Previous studies suggest an anti‐inflammatory effect of angiotensin II receptor blocker (ARB) treatment. The aim of this study was to compare the effect of ARB vs. placebo on plasma concentrations of inflammatory markers in HD patients. Methods: Adult HD patients were randomized for double‐blind treatment with the ARB irbesartan 150–300 mg/day or placebo. At baseline, 1 week, 3, 6, 9, and 12 months plasma high sensitivity C‐reactive protein (hsCRP), interleukin (IL)?1β, IL‐6, IL‐8, IL‐18, and transforming growth factor‐β (TGF‐β) were measured using Luminex and enzyme‐linked immunosorbent assay (ELISA) technology. Findings: Eighty‐two patients were randomized (placebo/ARB: 41/41). The groups did not differ in initial levels of any of the inflammatory markers (placebo/ARB median(range)): hsCRP 3.3(0.2–23.4)/2.7(0.2–29.6) μg/mL; IL‐1β 1.1(0.0–45.9)/1.1(0.0‐7.2) pg/mL; IL‐6 10(1–90)/12(1–84) pg/mL; IL‐8 31(9–134)/34(5–192) pg/mL; IL‐18 364(188–1343)/377(213–832) pg/mL; TGF‐β 3.2(0.8–13.9)/3.6(1.3–3.8) ng/mL. Overall, there was no significant difference in hsCRP, IL‐6, IL‐8, and TGF‐β between placebo and ARB‐treated patients during the study period, and hsCRP, IL‐6, IL‐8, and TGF‐β were relatively stable during the study period (P ≥ 0.18 in all tests for parallel curves, equal levels, and constant levels). The IL‐1β level was slightly different in the two groups over time, but not significantly (P = 0.09 in test for parallel curves) and it was also relatively stable during the study period (P ≥ 0.49 in tests for equal levels and constant level). IL‐18 was the only inflammatory marker which was not constant during the study period (P = 0.001 in test for constant level), but there was no significant difference between placebo and ARB‐treated (P ≥ 0.51 in tests for parallel curves and equal levels). Discussion: Inflammatory biomarkers were neither acutely, nor in the long‐term significantly affected by the ARB irbesartan. Our findings suggest that ARB treatment in HD patients does not offer protective anti‐inflammatory effects.     

Quality of life development during initial hemodialysis therapy and association with loss of residual renal function

Introduction: Health related quality of life (HRQOL) is markedly reduced in hemodialysis patients compared to the general population. We investigated the course of self‐reported HRQOL over time and the association with selected factors, focusing on changes in glomerular filtration rate (GFR). Methods: Eighty‐two newly started hemodialysis patients from the SAFIR cohort filled out the Kidney Disease Quality of Life Short Form Version 1.3 (KDQOL‐SF^TM) questionnaire at baseline, 6 and 12 months. The SAFIR study was a randomized, placebo‐controlled, double‐blind intervention study, examining the effects of the angiotensin II receptor blocker irbesartan. HRQOL was a secondary outcome measure. Main inclusion criteria: Dialysis vintage <1 year, left ventricular ejection fraction >30% and urinary output >300 mL/day. GFR was measured with mean creatinine and urea clearance from 24‐hour urine collections at baseline, 6 and 12 months. Findings: Irbesartan treatment did not affect HRQOL. Patients were pooled into one group for further analyses. Decline in GFR correlated significantly with decreasing HRQOL over time. HRQOL was stable over time, with a slight nonsignificant tendency toward improved HRQOL. The largest HRQOL‐differences (positive values equal improved HRQOL) observed during the 12 month study period were (mean[95% confidence interval]): Burden of kidney disease:6.4[?2.2;15.0], Role limitations‐physical:12.7[?2.1;27.5], and Role limitations‐emotional:9.7[?5.2;24.6]. Comorbidity, especially diabetes, hospital admissions, female gender, and age were strongly associated with lower HRQOL in cross sectional analysis. Discussion: Preservation of residual renal function seems to be important for HRQOL. In newly started HD patients, HRQOL showed little change after 12 months. HRQOL was negatively affected by comorbidity, especially diabetes, hospital admissions, female gender, and age.     

Understanding cost drivers of software evolution: a quantitative and qualitative investigation of change effort in two evolving software systems

Making changes to software systems can prove costly and it remains a challenge to understand the factors that affect the costs of software evolution. This study sought to identify such factors by investigating the effort expended by developers to perform 336 change tasks in two different software organizations. We quantitatively analyzed data from version control systems and change trackers to identify factors that correlated with change effort. In-depth interviews with the developers about a subset of the change tasks further refined the analysis. Two central quantitative results found that dispersion of changed code and volatility of the requirements for the change task correlated with change effort. The analysis of the qualitative interviews pointed to two important, underlying cost drivers: Difficulties in comprehending dispersed code and difficulties in anticipating side effects of changes. This study demonstrates a novel method for combining qualitative and quantitative analysis to assess cost drivers of software evolution. Given our findings, we propose improvements to practices and development tools to manage and reduce the costs.     

Dietary Fish Oil Alters DNA Methylation of Genes Involved in Polyunsaturated Fatty Acid Biosynthesis in Muscle and Liver of Atlantic Salmon (Salmo salar)

Adequate dietary supply of eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) is required to maintain health and growth of Atlantic salmon (Salmo salar). However, salmon can also convert α-linolenic acid (18:3n-3) into eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) by sequential desaturation and elongation reactions, which can be modified by 20:5n-3 and 22:6n-3 intake. In mammals, dietary 20:5n-3 + 22:6n-3 intake can modify Fads2 expression (Δ6 desaturase) via altered DNA methylation of its promoter. Decreasing dietary fish oil (FO) has been shown to increase Δ5fad expression in salmon liver. However, it is not known whether this is associated with changes in the DNA methylation of genes involved in polyunsaturated fatty acid synthesis. To address this, we investigated whether changing the proportions of dietary FO and vegetable oil altered the DNA methylation of Δ6fad_b, Δ5fad, Elovl2, and Elovl5_b promoters in liver and muscle from Atlantic salmon and whether any changes were associated with mRNA expression. Higher dietary FO content increased the proportions of 20:5n-3 and 22:6n-3 and decreased Δ6fad_b mRNA expression in liver, but there was no effect on Δ5fad, Elovl2, and Elovl5_b expression. There were significant differences between liver and skeletal muscle in the methylation of individual CpG loci in all four genes studied. Methylation of individual Δ6fad_b CpG loci was negatively related to its expression and to proportions of 20:5n-3 and 22:6n-3 in the liver. These findings suggest variations in dietary FO can induce gene-, CpG locus-, and tissue-related changes in DNA methylation in salmon.     

Increase in spinal stability obtained at levels of intra-abdominal pressure and back muscle activity realistic to work situations

In this study, sudden load was applied to the trunk and situations with alternating low levels of intra-abdominal pressure (IAP) realistic to work situations were compared. The aim was to see if IAP and the small increases in co-contraction of back muscles that follow are capable of increasing the stiffness of the lumbar spine. Nine subjects participated in ten sudden load situations during which they were asked to hold a box and conduct a percentage of maximal IAP. The hip was fixed and the load was applied horizontally on the trunk. EMG, IAP, and movement of the trunk were measured. It was found that IAP of a size likely to appear in work situations, and the concomitant increase in muscle co-activation increased the spine stiffness. This increase in stiffness decreased the movement caused by the sudden load. These results show that both abdominal- and back muscles may have an important role in stabilising the spine, and in decreasing movements caused by sudden loads likely to appear in numerous work     

Synchronously pumped optical parametric oscillation in periodically poled lithium niobate with 1-w average output power

We report on a rugged all-solid-state laser source of near-IR radiation in the range of 1461-1601 nm based on a high-power Nd:YVO(4) laser that is mode locked by a semiconductor saturable Bragg reflector as the pump source of a synchronously pumped optical parametric oscillator with a periodically poled lithium niobate crystal. The system produces 34-ps pulses with a high repetition rate of 235 MHz and an average output power of 1 W. The relatively long pulses lead to wide cavity detuning tolerances. The comparatively narrow spectral bandwidth of <15 GHz is suitable for applications such as pollutant detection.     

Biomechanical analysis of the effect of changing patient-handling technique

The objective of the study was to assess the changes in the mechanical load on the low-back when shifting from a self-chosen to a recommended patient-handling technique. Nine female health care workers without formal education in patient-handling carried out 8 different tasks involving moving, turning and lifting situations. By means of a dynamic 3D biomechanical model of the lower part of the body, peak torque, compression and shear forces at the L4/L5 joint were compared using the two different patient-handling techniques. In 5 of the 8 tasks, a significant reduction was observed in spinal loading. Application of the recommended technique decreased the compression value significantly for all tasks with a mean value above 3000 N. For the two tasks with the highest compression values when using the self-chosen technique (4223, 4446 N), the loading was reduced with 36% and 25%, respectively. If the principles behind the recommended technique are implemented and maintained, a decrease in the risk of low-back disorders during patient-handling should thus be expected.     

Effect of specific wavelengths on light-induced quality changes in Havarti cheese

The effects of exposure of slices of Havarti cheeses to monochromatic light of wavelengths 366 nm, 405 nm, and 436 nm, respectively, were studied by tristimulus colorimetry, solid-phase microextraction gas chromatographic analysis of volatiles, and open-end fluorescence spectroscopy. Having determined the photon fluxes of the three wavelengths by ferrioxalate actinometry, it was possible to quantify the effects of light exposure in an absolute manner. For all analyses, the most severe effects were caused by visible light, leading to colour bleaching, change in hue, riboflavin degradation, and formation of the secondary oxidation products hexanal, 1-pentanol, and 1-hexanol. Apparent quantum yields for formation of hexanal and 1-pentanol were found to be insignificantly different for 405 nm and 436 nm exposures, having values of (3-5) x 10(-5) mol x einstein(-1) and (9-13) x 10(-5) mol x einstein(-1), respectively. These compounds were not formed when exposed to 366 nm light. In contrast, 1-hexanol was formed when exposing cheese to all three wavelengths, resulting in apparent quantum yields of (2-6) x 10(-5) mol x einstein(-1). The results obtained are discussed in relation to the interplay between inherent product colorants, light sources, and transmission characteristics of the packaging materials.     

Self-switching in Mach-Zehnder interferometers with SOA phase shifters

A self-switching mechanism in Mach-Zehnder interferometers (MZIs) is described. The input light signal is distributed unequally over the interferometer arms using an multimode interference (MMI) coupler. In the arms, semiconductor optical amplifiers are placed as nonlinear phase shifters. Unequal intensities yield a nonlinear phase shift. The signals from the two arms are then recombined in an output MMI coupler. If an obtained nonlinear phase shift in the arms can compensate the coupler-induced phase difference between the arms, the signals are in phase at the output port. Choosing an appropriate output coupler, 2/spl times/1 and 2/spl times/2 devices can be obtained. The 2/spl times/2 and 2/spl times/1 MZIs can be used as pattern effect compensators and 2R-regenerators or low-loss combiner circuits, respectively. An active-passive integration technique is applied in order to realize the interferometric structures. Fabrication, simulation, and characterization of these devices are presented in this letter.