Breaking the trade-off between fast control and long lifetime of a superconducting qubit.

The rapid development in designs and fabrication techniques of superconducting qubits has made coherence times of qubits longer. In the future, however, the radiative decay of a qubit into its control line will be a fundamental limitation, imposing a trade-off between fast control and long lifetime of the qubit. Here, we break this trade-off by strongly coupling another superconducting qubit along the control line. This second qubit, which we call "Josephson quantum filter" (JQF), prevents the first qubit from emitting microwave photons and thus suppresses its relaxation, while transmitting large-amplitude control microwave pulses due to the saturation of the quantum filter, enabling fast qubit control. This device functions as an automatic decoupler between a qubit and its control line and could help in the realization of a large-scale superconducting quantum processor by reducing the heating of the qubit environment and the crosstalk between qubits.

Strong coupling of magnons in a YIG sphere to photons in a planar superconducting resonator in the quantum limit.

We report measurements made at millikelvin temperatures of a superconducting coplanar waveguide resonator (CPWR) coupled to a sphere of yttrium-iron garnet. Systems hybridising collective spin excitations with microwave photons have recently attracted interest for their potential quantum information applications. In this experiment the non-uniform microwave field of the CPWR allows coupling to be achieved to many different magnon modes in the sphere. Calculations of the relative coupling strength of different mode families in the sphere to the CPWR are used to successfully identify the magnon modes and their frequencies. The measurements are extended to the quantum limit by reducing the drive power until, on average, less than one photon is present in the CPWR. Investigating the time-dependent response of the system to square pulses, oscillations in the output signal at the mode splitting frequency are observed. These results demonstrate the feasibility of future experiments combining magnonic elements with planar superconducting quantum devices.

Peritoneal dialysis favorably influences early graft function after renal transplantation compared to hemodialysis.

BACKGROUND: Delayed graft function (DGF) and acute renal failure (ARF) after renal transplantation negatively influence short- and long-term graft outcome. Peritoneal dialysis as pretransplantation dialysis modality was reported to influence favorably the recovery of renal function immediately after kidney transplantation. It has been hypothesized that fluid status was the factor explaining this better outcome. This hypothesis was tested in this study by multivariate analysis, also including other factors related to DGF and ARF. METHODS: The records of peritoneal dialysis (PD; n=40) and hemodialysis (HD; n=79) patients receiving a first cadaveric kidney transplantation at the University Hospital Gent were analyzed. RESULTS: DGF and ARF were observed in 33 (27 HD and 6 PD, P=0.03) and 14 (14 HD and 0 PD, P=0.01) patients, respectively. The number of days needed to reach a serum creatinine 50% below that before transplantation (T1/2(SCr)), was correlated with cold ischemia time (CIT) (P<0.001) and body weight gain (BWG) (P<0.01) and was inversely correlated with urinary output in the first 24 hr (P<0.001), fluid load (P<0.001), and central venous pressure (P<0.001). A multivariate model with CIT (P<0.001), PD as pretransplantation dialysis mode (P=0.01), urinary output in the first 24 hr (P=0.001), BWG (P=0.05), and fluid load (P=0.01) resulted in an R2 of 0.32 (P<0.001). Using Cox regression analysis, the relative risk for a prolonged T1/2(SCr) increased with 4%/hr CIT (P=0.01) and with 1%/kg BWG (P=0.02). Fluid load decreased the relative risk with 5%/liter (P<0.001) and PD as pretransplantation modality favorably modified the relative risk by a factor of 1.6 (P=0.01). CONCLUSION: PD as pretransplantation dialysis modality can reduce the incidence and the severity of delayed recovery of renal function after renal transplantation. This protective effect was independent from CIT, and fluid status, two other major influencing factors.

The haematopoietic effect of recombinant human erythropoietin in haemodialysis is independent of the mode of administration (i.v. or s.c.).

BACKGROUND: Previous studies comparing intravenous (i.v.) and subcutaneous (s.c.) administration of recombinant human erythropoietin (rHuEpo) often did not achieve optimal iron reserve, were restricted to a limited follow-up period (not allowing equilibration) and/or did not exclude the role of other confounding factors. In addition all papers focused on the conversion from i.v. to s.c. METHODS: In this study, 30 equilibrated patients on s.c. rHuEpo were randomized into two groups, one converting to i.v. after 6 months of follow-up and one remaining on s.c. rHuEpo. In both groups rHuEpo was administered three times weekly. Only patients completing a further 6 months follow-up were considered for statistical evaluation. Serum ferritin was targeted at 200 ng/ml and haematocrits between 28 and 36% were pursued. RESULTS: The average haematocrit levels before conversion were 31.9 +/- 1.1% in the conversion group and 31.4 +/- 1.6% at the same time point in the nonconversion group (P = NS). After 6 months haematocrits were 31.5 +/- 0.5% in the conversion group and 31.1 +/- 0.9% in the non-conversion group (P = NS). Ferritin concentration in the conversion group was 219 +/- 49 ng/ml before and 230 +/- 83 ng/ml after the conversion. For the non-conversion group ferritin was 224 +/- 25 ng/ml and 236 +/- 52 ng/ml respectively (P = NS). The weight-standardized average rHuEpo dose per injection remained the same in the conversion group before and after conversion (44.0 +/- 1.8 U/kg/injection vs 45.4 +/- 4.7 U/kg/injection) (P = NS). In the non-conversion group the corresponding rHuEpo doses were 32.9 +/- 4.2 U/kg/injection and 39.6 +/- 7.0 U/kg/injection respectively (P = NS). There were no differences in serum PTH, aluminium, vitamin B12, folic-acid levels, and intake of co-trimoxazole, ACE inhibitors or theophylline. CONCLUSION: No changes in rHuEpo dose were observed after conversion from s.c. to i.v. There were no significant differences between the conversion and non-conversion group. These results are in contrast to some earlier studies suggesting lower rHuEpo requirements in case of s.c. administration.

Pretransplantation hemodialysis strategy influences early renal graft function.

The influence of the pretransplantation hemodialysis strategy on early renal graft function was evaluated in 44 patients receiving hemodialysis in the 24 h preceding kidney transplantation and in 13 patients receiving hemodialysis more than 24 h before transplantation. The patients dialyzed less than 24 h before transplantation were stratified according to treatment with or without complement-activating dialyzers (cuprophane, bioincompatible membrane [BICM] versus polysulfone, biocompatible membrane [BCM]) and with or without ultrafiltration (UF). Serum creatinine (Scr) at days 0, 2, 5, 10, and 30, the time for Scr to decrease 50% (T1/2Scr), the incidence of acute renal failure (ARF; defined as urinary volume < 500 ml/d and/or necessity for posttransplantation hemodialysis), and early graft dysfunction (defined as T1/2Scr > 3.5 d) were registered. Scr was higher in BCM- versus BICM-treated patients (P < 0.0001 by variance analysis) and in patients receiving UF versus those receiving no UF (P = 0.0009). T1/2Scr was higher in treatment with BICM versus BCM (7.4 +/- 7.9 versus 3.1 +/- 2.9 d; P < 0.05) and UF versus no UF (7.1 +/- 7.7 versus 2.7 +/- 2.0 d; P < 0.01). The evolution of Scr was markedly more favorable in the patient group treated with BCM without UF (T1/2Scr 1.7 +/- 0.8 d) compared with the group treated with BICM and UF (T1/2Scr 9.3 +/- 9.1 d; P < 0.01). The remaining groups (BICM without UF and BCM with UF) showed intermediate results. The incidence of ARF and early graft dysfunction was higher in the group on BICM with UF compared to BCM without UF. Functional differences persisted up to 1 mo after transplantation. Patients who underwent dialysis with UF more than 24 h before transplantation had a more beneficial evolution of renal function parameters than those who were dialyzed with UF less than 24 h before transplantation. In conclusion, the use of BICM and the application of UF within 24 h before kidney transplantation enhance the risk of posttransplantation ARF and early graft dysfunction.

Pharmacokinetics of recombinant hirudin in hemodialyzed end-stage renal failure patients.

Recently, hirudin was used for the first time as an anticoagulant during hemodialysis in men. Pharmacokinetic data of this compound in end-stage renal failure are however not available. In this study, the pharmacokinetics of recombinant hirudin (HBW 023) was evaluated in hemodialysis-treated end-stage renal failure patients. HBW 023 was administered as a bolus at the start of a single dialysis (0.02 to 0.08 mg/kg) in 20 patients, and plasma hirudin levels were followed during this and the 5 following dialyses, without additional hirudin administration. The initial dialysis (HD1) was performed with a low flux polysulfone dialyzer, the following dialyses (up to HD6) with a high flux polysulfone dialyzer and regular heparin. Hirudin levels averaged 504.0 +/- 214.0 and 527.7 +/- 217.1 ng/ml in the middle and at the end of HD1, and then gradually decreased to 15.2 +/- 15.2 ng/ml at the end of HD6. Pharmacokinetic data were compared to those obtained in healthy controls (n = 5), receiving the same dose, and reaching the same peak hirudin level. Hirudin half-life was > 30 times longer in hemodialysis patients (51.8 +/- 15.6 vs. 1.7 +/- 1.5 h, p < 0.001), whereas area under the curve was > 60 times higher (34,669 +/- 14,898 vs. 545 +/- 205 ng/ml x h, p < 0.001). Distribution volume was lower in hemodialysis patients (11.0 +/- 3.1 vs. 14.1 +/- 2.01, p < 0.05). Hirudin disappearance rate was the same during high flux polysulfone dialysis as during interdialytic periods. Hirudin removal was markedly higher in those patients still maintaining some residual renal function and parameters of hirudin removal were significantly correlated to residual creatinine clearance. It is concluded that hirudin removal from the body is markedly depressed in hemodialyzed end-stage renal failure patients and that even minor residual renal function may increase this removal rate.

Recombinant human erythropoietin corrects anaemia during the first weeks after renal transplantation: a randomized prospective study.

BACKGROUND: Studies on the effect of recombinant human erythropoietin (rHuEpo) on haematopoiesis in patients with kidney transplants, have been limited to progressive chronic graft failure, late after transplantation. In the present prospective randomized study, the efficacy of rHuEpo in the correction of anaemia during the first weeks after renal transplantation (RTP) was evaluated. METHODS: Patients were allocated to either an Epo- (n = 14) or a non-Epo-treated group (n = 15). Epo (150 U/kg.week s.c.) was started at a haematocrit (Hct) < 30% and was increased at weekly intervals by 30 U/kg.week, as long as Hct remained < 25%. RESULTS: In the Epo group, Hct increased from a nadir of 22 +/- 4% 2 weeks after RTP to 30 +/- 4% at week 4 and to 36 +/- 4% at week 6 (P < 0.001 and P < 0.0001 respectively vs week 2). Corresponding values in the non-Epo group were 25 +/- 6%, 28 +/- 6% (P = NS) and 32 +/- 6% (P < 0.05 vs week 2) (overall evolution Epo vs non-Epo: P = 0.038 by variance analysis). The differences in Hct between the Epo and non Epo group were even more marked in patients without major complications (variance analysis P = 0.009). The Epo-treated patients required fewer post-surgical blood transfusions (0.005 vs 0.014/days follow-up, P < 0.05), in spite of greater post-surgical blood losses, especially at day 1 (P < 0.05) and the presence of more major complications (7 vs 4) and a higher number of ganciclovir-treated patients (4 vs 0; P < 0.05). The maximum Epo dose after RTP was > 2x higher than the one required before RTP (197.1 +/- 45.1 vs 85.0 +/- 76.0 U/kg.week; P < 0.05). CONCLUSIONS: It is concluded that rHuEpo during the first weeks after RTP is of benefit in the correction of the Hct in the early post-surgical period, in spite of relative Epo resistance.

The utility of single-strand conformation polymorphism (SSCP) analysis: results obtained in families with Fabry's disease.

Single-strand conformation polymorphism (SSCP) analysis is a widely used and relatively simple method for detection of sequence polymorphisms in DNA fragments. We have used this technique to screen the alpha-galactosidase gene, with the aim of identifying the disease causing mutations in families with Fabry's disease. Five single-base shift mutations were found, but a single base-pair deletion could not be recognized by SSCP. The risk of mistaking a neutral polymorphism for a mutation is illustrated, and the utility as well as the limitations of SSCP in screening and diagnostic use are discussed.

Novel frameshift mutation in a heterozygous woman with Fabry disease and end-stage renal failure.

UNLABELLED: It is generally accepted that Fabry disease (angiokeratoma corporis diffusum) is an X-linked disorder resulting from the deficient activity of the lysosomal enzyme alpha-galactosidase. In males, the enzymatic defect leads to accumulation of glycosphingolipids, particularly in the kidney which causes end-stage renal disease. We report here a woman who presented in 1987 with focal and segmental glomerulosclerosis and required hemodialysis 4 years later when her son was evaluated for proteinuria. In these patients morphologic, biochemical, and genetic investigations were performed to explore the possibility of a hereditary renal disorder. Ultrastructural examination of the son's renal biopsy specimen revealed lamellated osmiophilic inclusions in the glomeruli, typical of Fabry disease. Four months after kidney transplantation in the mother, a graft biopsy specimen also revealed dense lamellated inclusions on electron microscopy. The leukocyte alpha-galactosidase activity was 0.008 mumol/min.10(9) cells in the son and 0.070 in the mother (range 0.100-0.500 mumol/min.10(9) cells). The diagnosis of Fabry disease was confirmed in both patients by the identification by DNA sequencing of a novel mutation in the alpha-galactosidase gene: one single base pair deletion in exon 3 (7317delA). IN CONCLUSION: (1) end-stage renal disease may occur in heterozygous women with Fabry disease; (2) morphologic lesions due to glycosphingolipid accumulation may be observed in the renal allograft after transplantation, and (3) DNA analysis confirmed the diagnosis by demonstrating a frameshift mutation, which has as yet not been reported.