Planar silicon pixel sensors with modified n\(^+\)-implantation shapes based on the IBL pixel sensor were designed in Dortmund. The sensors with a pixel size of \(250\,\mu\)m \(\times\) \(50\,\mu\)m ...are produced in n\(^+\)-in-n sensor technology. The charge collection efficiency should improve with electrical field strength maxima created by the different n\(^+\)-implantation shapes. Therefore, higher particle detection efficiencies at lower bias voltages could be achieved. The modified pixel designs and the IBL standard design are placed on one sensor to test and compare the designs. The sensor can be read out with the FE-I4 readout chip. At the iWoRiD 2018, measurements of sensors irradiated with protons and neutrons respectively at different facilities were presented and showed incongruent results. Unintended annealing during irradiation was considered as an explanation for the observed differences in the hit detection efficiency for two neutron irradiated sensors. This hypothesis will be examined and confirmed in this work, presenting first annealing studies of sensors irradiated with neutrons in Ljubljana.
The innermost part of the tracking detector of the ATLAS experiment consists mainly of planar n\(^+\)-in-n silicon pixel sensors. During the phase-0 upgrade, the Insertable B-Layer (IBL) was ...installed closest to the beam pipe. Its pixels are arranged with a pitch of \(250\,\mu\)m\(\,\times\,50\,\mu\)m with a rectangular shaped n\(^+\) implantation. Based on this design modified pixel designs have been developed in Dortmund. Six of these new pixel designs are arranged in structures of ten columns and were placed beside structures with the standard design on one sensor. Because of a special guard ring design, each structure can be powered and investigated separately. Several of these sensors were bump bonded to FE-I4 read-out chips. One of these modules was irradiated with reactor neutrons up to a fluence of \(5 \times 10^{15} \, n_{\text{eq}}\text{cm}^{-2}\). This contribution presents important sensor characteristics, charge collection determined with radioactive sources and hit efficiency measurements, performed in laboratory and test beam, of this irradiated device. It is shown that the new modified designs perform similar or better than the IBL standard design in terms of charge collection and tracking efficiency, at the cost of a slightly increased leakage current.
The effect of high-flux hemodialysis membranes on patient survival has not been unequivocally determined. In this prospective, randomized clinical trial, we enrolled 738 incident hemodialysis ...patients, stratified them by serum albumin < or = 4 and >4 g/dl, and assigned them to either low-flux or high-flux membranes. We followed patients for 3 to 7.5 yr. Kaplan-Meier survival analysis showed no significant difference between high-flux and low-flux membranes, and a Cox proportional hazards model concurred. Patients with serum albumin < or = 4 g/dl had significantly higher survival rates in the high-flux group compared with the low-flux group (P = 0.032). In addition, a secondary analysis revealed that high-flux membranes may significantly improve survival of patients with diabetes. Among those with serum albumin < or = 4 g/dl, slightly different effects among patients with and without diabetes suggested a potential interaction between diabetes status and low serum albumin in the reduction of risk conferred by high-flux membranes. In summary, we did not detect a significant survival benefit with either high-flux or low-flux membranes in the population overall, but the use of high-flux membranes conferred a significant survival benefit among patients with serum albumin < or = 4 g/dl. The apparent survival benefit among patients who have diabetes and are treated with high-flux membranes requires confirmation given the post hoc nature of our analysis.
Longer treatment time (TT) and slower ultrafiltration rate (UFR) are considered advantageous for hemodialysis (HD) patients. The study included 22 000 HD patients from seven countries in the Dialysis ...Outcomes and Practice Patterns Study (DOPPS). Logistic regression was used to study predictors of TT>240 min and UFR>10 ml/h/kg bodyweight. Cox regression was used for survival analyses. Statistical adjustments were made for patient demographics, comorbidities, dose of dialysis (Kt/V), and body size. Europe and Japan had significantly longer (P<0.0001) average TT than the US (232 and 244 min vs 211 in DOPPS I; 235 and 240 min vs 221 in DOPPS II). Kt/V increased concomitantly with TT in all three regions with the largest absolute difference observed in Japan. TT>240 min was independently associated with significantly lower relative risk (RR) of mortality (RR=0.81; P=0.0005). Every 30 min longer on HD was associated with a 7% lower RR of mortality (RR=0.93; P<0.0001). The RR reduction with longer TT was greatest in Japan. A synergistic interaction occurred between Kt/V and TT (P=0.007) toward mortality reduction. UFR>10 ml/h/kg was associated with higher odds of intradialytic hypotension (odds ratio=1.30; P=0.045) and a higher risk of mortality (RR=1.09; P=0.02). Longer TT and higher Kt/V were independently as well as synergistically associated with lower mortality. Rapid UFR during HD was also associated with higher mortality risk. These results warrant a randomized clinical trial of longer dialysis sessions in thrice-weekly HD.
We present a comprehensive, high-quality dataset characterizing soil-vegetation and land surface processes from continuous measurements conducted in two climatically contrasting study regions in ...southwestern Germany: the warmer and drier Kraichgau region with a mean temperature of 9.7 .sup." C and annual precipitation of 890 mm and the cooler and wetter Swabian Alb with mean temperature 7.5 .sup." C and annual precipitation of 1042 mm. In each region, measurements were conducted over a time period of nine cropping seasons from 2009 to 2018. The backbone of the investigation was formed by six eddy-covariance (EC) stations which measured fluxes of water, energy and carbon dioxide between the land surface and the atmosphere at half-hourly resolution. This resulted in a dataset containing measurements from a total of 54 site years containing observations with a multitude of crops, as well as considerable variation in local growing-season climates.
Background. Current methods of renal replacement therapy lead only to an insignificant removal of larger, potentially toxic, substances, which are excreted by healthy kidneys. On‐line preparation of ...substituate from dialysate and the use of high‐flux membranes allow substantial convective removal of such substances. A modified on‐line haemodiafiltration method with the use of a large membrane surface and a high convective part was chosen to test whether the elimination of larger substances, such as low‐ molecular‐mass proteins, has a clinical impact. Methods. In a prospective, controlled study over 24 months, 44 unselected chronic dialysis patients were randomized to undergo either low‐flux haemodialysis (HD; n=21) or haemodiafiltration (HDF; n=23). To eliminate confounding factors, low‐molecular efficacy was matched (Kt/V 1.8), and the same membrane material (polysulfone), ultrapure dialysate and the same treatment duration (4.5 h) were applied to each group. Results. Morbidity, mortality, blood pressure, dialysis‐associated hypotensive episodes, haematocrit and erythropoietin dose did not differ between the groups. The same was true for body weight and, accordingly, bioimpedance values, clinical hydration score, skinfold thickness, plasma albumin, prealbumin and transferrin. β2‐Microglobulin in the plasma did not change in the HD group and varied between 32 and 43 mg/l throughout the 2 years. In HDF β2 microglobulin decreased from similar values to 18 mg/l predialysis (P<0.01) in the first 6 months of HDF treatment and then remained constant during the remaining 18 months. Conclusion. In the absence of any clinical marker of uraemic toxicity the removal of larger molecules over the time‐span of 2 years during HDF had no clinical implication compared with extremely (and for routine practice unrealistically) well‐dialysed patients with low‐flux HD. In the absence of any side‐effects of on‐line HDF and supposing that plasma β2‐microglobulin is a marker of morbidity, on‐line HDF ensures an excellent dialysis quality which apparently takes time to translate into measurable clinical sequelae.
Abstract
Background and objectives:
C.E.R.A., a continuous erythropoietin receptor activator, offers once-monthly dosing without compromising haemoglobin control. This study was undertaken to examine ...whether monthly C.E.R.A. using pre-filled syringes maintains stable haemoglobin levels when administered according to local clinical judgement.
Research, design and methods:
MIRACEL was a prospective, open-label, single-arm, multicentre study performed at 90 nephrology centres in Germany. After a 2-month screening phase, haemodialysis patients receiving epoetin or darbepoetin were converted to monthly intravenous C.E.R.A., with a 5-month titration phase followed by a 2-month evaluation phase.
Clinical trial registration:
Clinicaltrials.gov: NCT00413894
Results:
Of 661 patients screened, 424 (64.1%) started C.E.R.A. therapy (previous treatment: 72.2% epoetin, 27.8% darbepoetin); 416 were eligible for inclusion in the intent-to-treat population. A mean of two C.E.R.A. dose changes were required during the 7-month treatment period. The primary efficacy variable, haemoglobin within 11-12.5 g/dL or 10-13 g/dL during the evaluation phase, was achieved in 109 (30.8%) and 265 (74.9%) of the 354 evaluable patients, respectively, with no differences observed between patients formerly receiving epoetin or darbepoetin or different dosing frequencies. During the screening, titration and evaluation phases, mean haemoglobin was 11.7 0.7 g/dL, 11.6 0.9 g/dL and 11.4 1.0 g/dL, respectively, and 90.6% (377/416), 70.4% (293/416) and 82.9% (345/416) of patients exhibited ≤ 1 g/dL change from phase-specific individual means. C.E.R.A. was well-tolerated with a safety profile similar to that reported in phase III studies.
Conclusions:
In this single-arm, open-label, multicentre study, conversion of a large population of haemodialysis patients from epoetin or darbepoetin to monthly C.E.R.A. administration using pre-filled syringes was shown to be practical, convenient and offer good control of haemoglobin levels, regardless of the previous type of therapy or dosing frequency.
Background. Repetitive exposure to cytokine‐inducing substances (pyrogens) results in chronic inflammation, which may significantly contribute to some of the long‐term complications in dialysis ...patients. On‐line dialysis modalities, such as on‐line haemodiafiltration (HDF), raise particular concerns because of the administration of infusate prepared from potentially contaminated dialysis fluid. Hence, great retention capability for pyrogens is of critical importance for the safe performance of on‐line systems. Methods. The microbiological safety of a novel on‐line system, ONLINEplus™, was assessed in clinical practice in five centres for 3 months. Infusate and dialysis fluid were regularly monitored for microbial counts, endotoxins, and cytokine‐inducing activity. Levels of interleukin‐1 receptor antagonist (IL‐1Ra) were determined in supernatants of whole blood incubated either under pyrogen‐free conditions (spontaneous cytokine production) or following low‐dose endotoxin exposure (LPS‐stimulated cytokine production). Results. We failed to detect microorganisms or endotoxin contamination of infusate during the entire study period. Moreover, neither infusate nor dialysis fluid demonstrated cytokine‐inducing activity. Intradialytic IL‐1Ra induction was not detected, as there was no difference between pre‐ and post‐session values for both spontaneous and LPS‐stimulated IL‐1Ra production (115±26 vs 119±27 and 2445±353 vs 2724±362 pg/106 white blood cells (WBC), respectively). Neither the number of immunocompetent cells nor their capacity to produce IL‐1Ra declined during this period, indicating that cells were not significantly stimulated during treatment. Spontaneous and LPS‐induced exvivo IL‐1Ra generation remained unchanged after 3 months of on‐line HDF therapy as compared with the start of the study (71±30 pre‐ vs 48±14 post‐study, and 2559±811 vs 2384±744 pg/106 WBC, respectively). Conclusions. The present on‐line system performed safely from a microbiological view‐point as both the dialysis fluid and infusate were consistently free of microorganisms, endotoxins, and cytokine‐inducing substances. As a result, on‐line HDF therapy had no effect upon the chronic inflammatory responses in end‐stage renal disease patients.
Background:
Medications affect many measures of hemodialysis patients’ well-being.
Methods:
The Dialysis Outcomes and Practice Patterns Study (DOPPS) has evaluated the use of hydroxymethyl glutaryl ...coenzyme A reductase inhibitors (statins), analgesics, antidepressants, and multivitamins. Additionally, DOPPS has reported on the associations between vascular access outcomes and related medications.
Results:
Prescription of statins varied widely across countries, with the highest use in the United States. Patients prescribed statins had lower risk of cardiac and noncardiac causes of mortality than those who were not prescribed statins. DOPPS data also show that statins are underprescribed relative to recent Kidney Disease Outcomes Quality Initiative guidelines. No guidelines have been established for analgesic use, but high pain levels self-reported by hemodialysis patients suggest opportunities for improved pain management strategies. Guidelines for analgesic use in dialysis patients may help balance improved quality of life against potential side effects of analgesics. Medical and patient questionnaires show that depression in hemodialysis patients is common, frequently underdiagnosed, usually untreated, and associated with increased rates of mortality and hospitalization. Calcium channel blockers were associated with improved primary graft patency, aspirin with improved secondary graft patency, and angiotensin-converting enzyme inhibitors with improved secondary fistula patency. All 3 medications were associated with significantly decreased relative risk for access failure. There is large country variation in multivitamin use, with significantly higher use in the United States compared with Europe and Japan. Patients taking multivitamins had lower mortality risk than patients not taking multivitamins.
Conclusion:
DOPPS findings on medications indicate that prospective trials are needed before guidelines can be developed for appropriate medication use in these different therapeutic categories.
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