| 1. |
- Webb, Nicholas J A, et al.
(författare)
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Multicentre prospective randomised trial of tacrolimus, azathioprine and prednisolone with or without basiliximab: two-year follow-up data.
- 2009
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Ingår i: Pediatric nephrology (Berlin, Germany). - : Springer Science and Business Media LLC. - 0931-041X .- 1432-198X. ; 24:1, s. 177-82
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Tidskriftsartikel (refereegranskat)abstract
- A total of 192 children and adolescents undergoing renal transplantation were randomly chosen to receive tacrolimus, azathioprine and corticosteroids (TAS, n = 93) or tacrolimus, azathioprine, corticosteroids and two doses of basiliximab (TAS + B, n = 99). Six-month outcome data have previously been reported; this manuscript reports the 2-year data. Complete 2-year data were available on 164 (85.4%) of the original 192 patients. There was a single death in the TAS arm. Kaplan-Meier estimates of survival free of graft loss at 2 years were 94.9% in the TAS + B arm and 89.6% in the TAS arm [hazard ratio (HR) 0.52; 95% confidence interval (CI) 0.17 to 1.54, P = 0.23]. Estimates of survival free from rejection at 2 years were 75.2% in the TAS + B arm and 68.7% in the TAS arm (HR 0.81; 95% CI 0.46 to 1.40, P = 0.44). The mean estimated glomerular filtration rate (GFR) at 2 years, was 65.8 ml/min per 1.73 m(2) body surface area in the TAS arm and 66.7 ml/min per 1.73 m(2) in the TAS + B arm (P = 0.78). Blood pressure and cholesterol levels were similar in the two arms, and there was no evidence of a difference in the incidence of infection or malignancy. These data provide further evidence of a lack of benefit associated with the addition of basiliximab to a TAS regimen for European paediatric renal transplant recipients at low immunological risk.
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| 2. |
- Harker, Geraint J. A., et al.
(författare)
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Detection and extraction of signals from the epoch of reionization using higher-order one-point statistics
- 2009
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 393, s. 1449-1458
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Tidskriftsartikel (refereegranskat)abstract
- Detecting redshifted 21-cm emission from neutral hydrogen in the early Universe promises to give direct constraints on the epoch of reionization (EoR). It will, though, be very challenging to extract the cosmological signal (CS) from foregrounds and noise which are orders of magnitude larger. Fortunately, the signal has some characteristics which differentiate it from the foregrounds and noise, and we suggest that using the correct statistics may tease out signatures of reionization. We generate mock data cubes simulating the output of the Low Frequency Array (LOFAR) EoR experiment. These cubes combine realistic models for Galactic and extragalactic foregrounds and the noise with three different simulations of the CS. We fit out the foregrounds, which are smooth in the frequency direction, to produce residual images in each frequency band. We denoise these images and study the skewness of the one-point distribution in the images as a function of frequency. We find that, under sufficiently optimistic assumptions, we can recover the main features of the redshift evolution of the skewness in the 21-cm signal. We argue that some of these features - such as a dip at the onset of reionization, followed by a rise towards its later stages - may be generic, and give us a promising route to a statistical detection of reionization.
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| 3. |
- Thomas, Rajat M., et al.
(författare)
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Fast large-scale reionization simulations
- 2009
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 393, s. 32-48
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Tidskriftsartikel (refereegranskat)abstract
- We present an efficient method to generate large simulations of the epoch of reionization without the need for a full three-dimensional radiative transfer code. Large dark-matter-only simulations are post-processed to produce maps of the redshifted 21-cm emission from neutral hydrogen. Dark matter haloes are embedded with sources of radiation whose properties are either based on semi-analytical prescriptions or derived from hydrodynamical simulations. These sources could either be stars or power-law sources with varying spectral indices. Assuming spherical symmetry, ionized bubbles are created around these sources, whose radial ionized fraction and temperature profiles are derived from a catalogue of one-dimensional radiative transfer experiments. In case of overlap of these spheres, photons are conserved by redistributing them around the connected ionized regions corresponding to the spheres. The efficiency with which these maps are created allows us to span the large parameter space typically encountered in reionization simulations. We compare our results with other, more accurate, three-dimensional radiative transfer simulations and find excellent agreement for the redshifts and the spatial scales of interest to upcoming 21-cm experiments. We generate a contiguous observational cube spanning redshift 6 to 12 and use these simulations to study the differences in the reionization histories between stars and quasars. Finally, the signal is convolved with the Low Frequency Array (LOFAR) beam response and its effects are analysed and quantified. Statistics performed on this mock data set shed light on possible observational strategies for LOFAR.
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| 4. |
- Grenda, R., et al.
(författare)
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A prospective, randomized, multicenter trial of tacrolimus-based therapy with or without basiliximab in pediatric renal transplantation
- 2006
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Ingår i: American journal of transplantation. - : Elsevier BV. - 1600-6135. ; 6:7, s. 1666-72
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Tidskriftsartikel (refereegranskat)abstract
- In a 6-month, multicenter, randomized, controlled, open-label, parallel-group trial, we investigated the efficacy and safety of adding basiliximab to a standard tacrolimus-based regimen in pediatric renal transplant recipients. Patients < 18 years received tacrolimus/azathioprine/steroids (TAS, n = 93) or tacrolimus/azathioprine/steroids/basiliximab (TAS + B, n = 99). Target tacrolimus levels were 10-20 ng/mL between days 0-21 and 5-15 ng/mL thereafter. Steroid dosing was identical in both groups. Basiliximab was administered at 10 mg (patients < 40 kg) or 20 mg (patients > or = 40 kg) within 4 h of reperfusion; the same dose was repeated on day 4. Biopsy-proven acute rejection rates were 20.4% (TAS) and 19.2% (TAS + B); steroid-resistant acute rejection rates were 3.2% and 3.0%, respectively. Patient survival was 100%; graft survival rates were 95% in both arms. The nature and incidence of adverse events were similar in both arms except toxic nephropathy and abdominal pain, which were significantly higher in the TAS + B arm (14.1% vs. 4.3%; p = 0.03 and 11.1% vs. 2.2%; p = 0.02; respectively). Median serum creatinine concentrations at 6 months were 86 micromol/L in the TAS and 91 micromol/L in the TAS + B arm; glomerular filtration rate was 79.4 and 77.6 (mL/min/1.73 m2), respectively. Adding basiliximab to a tacrolimus-based regimen is safe in pediatric patients, but does not improve clinical efficacy.
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| 5. |
- Harker, Geraint, et al.
(författare)
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Non-parametric foreground subtraction for 21-cm epoch of reionization experiments
- 2009
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 397, s. 1138-1152
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Tidskriftsartikel (refereegranskat)abstract
- One of the problems facing experiments designed to detect redshifted 21-cm emission from the epoch of reionization (EoR) is the presence of foregrounds which exceed the cosmological signal in intensity by orders of magnitude. While fitting them so that they can be removed, we must be careful to minimize `overfitting', in which we fit away some of the cosmological signal, and `underfitting', in which real features of the foregrounds cannot be captured by the fit, polluting the signal reconstruction. We argue that in principle it would be better to fit the foregrounds non-parametrically - allowing the data to determine their shape - rather than selecting some functional form in advance and then fitting its parameters. Non-parametric fits often suffer from other problems, however. We discuss these before suggesting a non-parametric method, Wp smoothing, which seems to avoid some of them. After outlining the principles of Wp smoothing, we describe an algorithm used to implement it. Some useful results for implementing an alternative algorithm are given in an appendix. We apply Wp smoothing to a synthetic data cube for the Low Frequency Array (LOFAR) EoR experiment. This cube includes realistic models for the signal, foregrounds, instrumental response and noise. The performance of Wp smoothing, measured by the extent to which it is able to recover the variance of the cosmological signal and to which it avoids the fitting residuals being polluted by leakage of power from the foregrounds, is compared to that of a parametric fit, and to another non-parametric method (smoothing splines). We find that Wp smoothing is superior to smoothing splines for our application, and is competitive with parametric methods even though in the latter case we may choose the functional form of the fit with advance knowledge of the simulated foregrounds. Finally, we discuss how the quality of the fit is affected by the frequency resolution and range, by the characteristics of the cosmological signal and by edge effects.
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| 6. |
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| 7. |
- Granqvist, Anna, et al.
(författare)
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Podocyte proteoglycan synthesis is involved in the development of nephrotic syndrome
- 2006
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Ingår i: Am J Physiol Renal Physiol. - : American Physiological Society. - 0363-6127 .- 1931-857X .- 1522-1466. ; 291
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Tidskriftsartikel (refereegranskat)abstract
- Proteoglycans (PG) are important for the glomerular barrier, for cell signaling and for the anchorage of cells to the glomerular basement membrane. They are, however, complex macromolecules, and their production has not yet been thoroughly investigated for podocytes. In the present study, we have studied the biosynthesis of proteoglycans by highly differentiated human podocytes and in rats. The cells were treated with puromycin aminonucleoside (PAN, a nephrosis inducing agent), steroids (used as primary treatment for nephrotic syndrome) or both. Analysis was made by Taqman(R)real-time PCR, Western blot and by metabolic labeling with (35)S and (3)H. We found that podocytes produce versican, syndecan-1, decorin and biglycan together with the previously known PGs syndecan-4, glypican and perlecan. PAN treatment down-regulated the mRNA and the protein expression of both versican (by 24+/-6%, p<0.01, for mRNA and by 50% for protein) and perlecan (by 14+/-5%, p<0.05, for mRNA and by 50% for protein). The decreased expression was confirmed by studying the glomerular gene expression in rats treated with PAN during a time course study. In addition, puromycin decreased the expression of enzymes involved in the glycosaminoglycan (GAG) biosynthesis. Steroid treatment decreased perlecan (by 24+/-3%, p<0.01) and syndecan-1 expression (by 30+/-4%, p<0.01), but increased the expression of decorin 2.5-fold. The observed alterations of proteoglycan synthesis induced by PAN may lead to decreased glomerular anionic charge and disturbed podocyte morphology, factors that are important for the development of a nephrotic syndrome.
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| 8. |
- Harker, Geraint J. A., et al.
(författare)
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Detection and extraction of signals from the epoch of reionization using higher order one-point statistics
- 2008
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Detecting redshifted 21cm emission from neutral hydrogen in the early Universe promises to give direct constraints on the epoch of reionization (EoR). It will, though, be very challenging to extract the cosmological signal from foregrounds and noise which are orders of magnitude larger. Fortunately, the signal has some characteristics which differentiate it from the foregrounds and noise, and we suggest that using the correct statistics may tease out signatures of reionization. We generate mock datacubes simulating the output of the LOFAR EoR experiment. These cubes combine realistic models for Galactic and extragalactic foregrounds and the noise with three different simulations of the cosmological signal. We fit out the foregrounds, which are smooth in the frequency direction, to produce residual images in each frequency band. We denoise these images and study the skewness of the one-point distribution in the images as a function of frequency. We find that, under sufficiently optimistic assumptions, we can recover the main features of the redshift evolution of the skewness in the 21cm signal. We argue that some of these features - such as a dip at the onset of reionization, followed by a rise towards its later stages - may be generic, and give us a promising route to a statistical detection of reionization.
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| 9. |
- Manea Hedström, Minola, et al.
(författare)
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Podocytes express ADAMTS13 in normal renal cortex and in patients with thrombotic thrombocytopenic purpura
- 2007
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 138:5, s. 651-662
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Tidskriftsartikel (refereegranskat)abstract
- Congenital thrombotic thrombocytopenic purpura (TTP) is associated with ADAMTS13 mutations. The major site of ADAMTS13 synthesis is the liver. Expression in other tissues, and in TTP, has not been shown. In this study, ADAMTS13 protein expression was investigated in normal kidney and in renal tissue from two TTP patients, with a compound heterozygous mutation (P353L and P457L) and a homozygous mutation (4143insA). Real-time polymerase chain reaction demonstrated ADAMTS13 mRNA in normal kidney. ADAMTS13 was detected in the glomeruli and tubuli of normal and TTP kidney using anti-ADAMTS13 antibodies. In the glomeruli, expression was localised to podocytes (as demonstrated by counterstaining with two podocyte markers) and endothelium. Similar distribution was detected in the TTP kidneys. Electron microscopy detected ADAMTS13 in podocytes, endothelium and glomerular basement membrane. Cultured human podocytes expressed ADAMTS13 mRNA and protein, and podocyte lysate exhibited von Willebrand factor-cleaving activity. Mutation expression studies of the P353L and P457L mutations showed partially impaired secretion and lower activity of the secreted mutants. Impaired secretion has previously been shown for the 4143insA mutation. Podocyte-derived ADAMTS13 may offer local protection in the high-shear microcirculation of the glomerulus. The mutations in the two TTP patients studied enabled protein expression in the podocytes but affected protease secretion.
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| 10. |
- Nyström, Jenny, 1972, et al.
(författare)
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CRIM1 is localized to the podocyte filtration slit diaphragm of the adult human kidney
- 2009
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Ingår i: Nephrol Dial Transplant. - : Oxford University Press (OUP). - 1460-2385 .- 1460-2385 .- 0931-0509. ; 24:7, s. 2038-44
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: CRIM1 is a plasma membrane bound protein containing six cysteine-rich repeats (CRR). Through these, CRIM1 has been shown to interact with a subgroup of the TGF-beta superfamily, the bone morphogenic proteins (BMP) isoforms 2, 4 and 7. The probable action is to modulate the signalling properties of these factors. CRIM1 has also been shown to regulate the release of VEGFA by podocytes during renal organogenesis. Knock-out studies in mice have shown that CRIM1 is critically involved in the development of the central nervous system, eye and kidney. Replacement of CRIM1 with a defective version leads to renal dysgenesis and perinatal death. We have analysed the distribution of CRIM1 in adult human renal tissue. METHODS: To this end, we have used immunofluorescence, immunohistochemistry and immunoelectron microscopy. We performed western blotting for the CRIM1 protein, using lysates from isolated glomerular podocytes and human renal tissue homogenate. By using quantitative PCR, we compared the CRIM1 mRNA levels in podocytes, human renal tissue homogenate, primary human renal proximal tubular epithelial cells and primary human pulmonary artery smooth muscle cells. RESULTS: The results show that in the human adult kidney, CRIM1 is mainly expressed in the glomerular podocytes and is associated with the insertional region of the filtration slit diaphragm (SD) of the podocyte pedicles. CONCLUSIONS: CRIM1 is a protein that should be added to the list of proteins associated with the podocyte filtration SD and with the probable action of modulating BMP and VEGFA signalling.
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| 11. |
- Qader, Saleem, et al.
(författare)
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Could Quality of Life Impact the Prevalence of Metabolic Syndrome? Results from a Population-Based Study of Swedish Women: The Women's Health in the Lund Area Study.
- 2008
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Ingår i: Metabolic syndrome and related disorders. - : Mary Ann Liebert Inc. - 1557-8518 .- 1540-4196.
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background: The metabolic syndrome is regarded as an important risk factor for diabetes mellitus and cardiovascular disease. Metabolic syndrome could be associated with impaired quality of life (QoL). Methods: The Women's Health in the Lund Area (WHILA) project covers 10,766 women born between December 2, 1935, and December 1, 1945, living in the Lund area, of Sweden by December 1, 1995. The primary objectives of this project were to survey perimenopausal women in this area and to evaluate their health status and lifestyles. We used the criteria for the metabolic syndrome, as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III), which include three or more of five risk factors: central obesity, elevated serum triglycerides, low high-density lipoprotein cholesterol (HDL-C), and elevated blood pressure and fasting glucose. Analysis of most aspects of daily life and QoL according to the Gothenburg Quality of Life Instrument (GQL) was done. GQL refers to the WHO definition of health. Results: A total number of 6913 (64.2%) women with a mean age (56.1) years fulfilled the criteria for screening procedure in the WHILA study. A positive association between women with metabolic syndrome and the following aspects of quality of life were found: "Partnership," "free time," "memory," and being "appreciated outside home." However, "economy," "health," "body image," and "fitness" had a negative association to the metabolic syndrome. Conclusion: QoL is an important factor for metabolic syndrome. Apart from traditional biological factors, prevention of metabolic syndrome should also encompass QoL.
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