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- Winkler, TW, et al.
(författare)
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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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- Abel, I, et al.
(författare)
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Overview of the JET results with the ITER-like wall
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
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Tidskriftsartikel (refereegranskat)abstract
- Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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- Fischler, B, et al.
(författare)
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Incidence, Impact and Treatment of Ongoing CMV Infection in Patients with Biliary Atresia in Four European Centres
- 2022
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Cytomegalovirus (CMV) infection has been suggested to be of importance for the development and outcome of biliary atresia (BA). However, most data are only available from single centre studies. We retrospectively collected data on rates, outcomes, and treatments for ongoing CMV infection at the time of Kasai portoenterostomy (KPE) from four different tertiary centres in Europe. The rate of ongoing CMV infection varied between 10–32% in the four centres. CMV positive patients were significantly older and had higher levels of several liver biochemistries at the time of KPE (p < 0.05 for all comparisons). In the largest centre, CMV infection was more common in non-Caucasians, and CMV infected patients had poorer long-term survival with native liver than CMV negative patients (p = 0.0001). In contrast, survival with native liver in the subgroup of CMV infected patients who had received antiviral treatment was similar to the CMV negative group. We conclude that ongoing CMV infection at the time of KPE occurs in a significant proportion of BA patients and that these patients seem to differ from CMV negative patients regarding age and biochemistry at the time of KPE as well as long-term survival with native liver. The latter difference may be reduced by antiviral treatment, but randomized, controlled trials are needed before such treatment can be recommended routinely.
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- Knaapen, M, et al.
(författare)
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Establishing a core outcome set for treatment of uncomplicated appendicitis in children: study protocol for an international Delphi survey
- 2019
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:5, s. e028861-
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Tidskriftsartikel (refereegranskat)abstract
- Appendicitis is a global disease affecting roughly 1 in every 12 people in the world, with the highest incidence between ages 10 and 19 years. To date, a wide variety of health outcomes have been reported in randomised controlled trials and meta-analyses evaluating treatments for appendicitis. This is especially the case in studies comparing non-operative treatment with operative treatment. A set of standard outcomes, to be reported in all future trials, is needed to allow for adequate comparison and interpretation of clinical trial results and to make data pooling possible. This protocol describes the development of such a global core outcome set (COS) to allow unified reporting of treatment interventions in children with acute uncomplicated appendicitis.Methods and analysisWe use current international standard methodology for the development and reporting of this COS. Its development consists of three phases: (1) an update of the most recent systematic review on outcomes reported in uncomplicated paediatric appendicitis research to identify additional outcomes, (2) a three-step global Delphi study to identify a set of core outcomes for which there is consensus between parents and (paediatric) surgeons and (3) an expert meeting to finalise the COS and its definitions. Children and young people will be involved through their parents during phase 2 and will be engaged directly using a customised face-to-face approach.Ethics and disseminationThe medical research ethics committee of the Academic Medical Center Amsterdam has approved the study. Each participating country/research group will ascertain ethics board approval. Electronic informed consent will be obtained from all participants. Results will be presented in peer-reviewed academic journals and at (international) conferences.Trial registration numberCOMET registration: 1119
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- Maita, S, et al.
(författare)
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Nonoperative treatment for nonperforated appendicitis in children: a systematic review and meta-analysis
- 2020
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Ingår i: Pediatric surgery international. - : Springer Science and Business Media LLC. - 1437-9813 .- 0179-0358. ; 36:3, s. 261-269
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Tidskriftsartikel (refereegranskat)abstract
- Acute appendicitis is the most common surgical emergency in children. Nonoperative treatment of nonperforated acute appendicitis in children is an alternative to appendectomy. The purpose of this systematic review and meta-analysis was to determine the outcomes of nonoperative treatment of nonperforated acute appendicitis in children in the literature. Databases were searched to identify abstracts, using predefined search terms. The abstracts were reviewed by two independent reviewers and articles were selected according to inclusion and exclusion criteria. Data were extracted by the two reviewers and analyzed. The literature search yielded 2743 abstracts. Twenty-one articles were selected for analysis. The study design was heterogenous, with only one randomized controlled study. The symptoms resolved in 92% [95% CI (88; 96)] of the nonoperatively treated patients. Meta-analysis showed that an additional 16% (95% CI 10; 22) of patients underwent appendectomy after discharge from initial hospital stay. Complications and length of hospital stay was not different among patients treated with antibiotics compared with those who underwent appendectomy. Nonoperative treatment of nonperforated acute appendicitis children is safe and efficient. There is a lack of large randomized controlled trials to compare outcomes of nonoperative treatment with appendectomy.
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| 32. |
- Milao, JF, et al.
(författare)
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Natural killer cells induce HIV-1 latency reversal after treatment with pan-caspase inhibitors
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 1067767-
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Tidskriftsartikel (refereegranskat)abstract
- The establishment of a latency reservoir is the major obstacle for a cure of HIV-1. The shock-and-kill strategy aims to reactivate HIV-1 replication in HIV -1 latently infected cells, exposing the HIV-1-infected cells to cytotoxic lymphocytes. However, none of the latency reversal agents (LRAs) tested so far have shown the desired effect in people living with HIV-1. We observed that NK cells stimulated with a pan-caspase inhibitor induced latency reversal in co-cultures with HIV-1 latently infected cells. Synergy in HIV-1 reactivation was observed with LRAs prostratin and JQ1. The supernatants of the pan-caspase inhibitor-treated NK cells activated the HIV-1 LTR promoter, indicating that a secreted factor by NK cells was responsible for the HIV-1 reactivation. Assessing changes in the secreted cytokine profile of pan-caspase inhibitor-treated NK cells revealed increased levels of the HIV-1 suppressor chemokines MIP1α (CCL3), MIP1β (CCL4) and RANTES (CCL5). However, these cytokines individually or together did not induce LTR promoter activation, suggesting that CCL3-5 were not responsible for the observed HIV-1 reactivation. The cytokine profile did indicate that pan-caspase inhibitors induce NK cell activation. Altogether, our approach might be–in combination with other shock-and-kill strategies or LRAs–a strategy for reducing viral latency reservoirs and a step forward towards eradication of functionally active HIV-1 in infected individuals.
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| 38. |
- Romanelli, F, et al.
(författare)
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Overview of the JET results
- 2011
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
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Tidskriftsartikel (refereegranskat)abstract
- Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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| 39. |
- Schmidt, DC, et al.
(författare)
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The evolution of interstitial-type defects in silicon during platinum diffusion from 400 to 600 degrees C following 2-MeV electron irradiation
- 1999
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Ingår i: Materials Science & Engineering. - 0921-5107 .- 1873-4944. ; 68:2, s. 67-71
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Tidskriftsartikel (refereegranskat)abstract
- Platinum has been diffused into epitaxial n-type silicon for 30 min at temperatures from 400 to 600 degrees C following room temperature irradiation with 2-MeV electrons at a dose of 1 x 10(17) e(-) cm(-2). Platinum has only been detected by deep level transient spectroscopy (DLTS) following the highest diffusion temperature. For lower temperatures defects, not previously reported. arise which are thought to be of interstitial nature. The two principal defect levels are determined to be located at 0.29 and 0.41 eV below the conduction band. The compensation for the two lowest diffusion temperatures is observed to be extremely strong as manifested by a strong reduction of the steady state reverse bias capacitance during the DLTS measurements. Following thermal treatment at 500 degrees C this capacitance, however, increases. DLTS measurements down to 20 K detected thermal donors as well as a number of other defects not previously reported. Their signatures have been determined by DLTS and TSCap (thermally stimulated capacitance) measurements. The nature of the observed defects is discussed with reference to recent results concerning interstitial defects. (C) 1999 Elsevier Science S.A. All rights reserved.
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| 42. |
- Svensson, JF, et al.
(författare)
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A review of conservative treatment of acute appendicitis
- 2012
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Ingår i: European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie. - : Georg Thieme Verlag KG. - 1439-359X. ; 22:3, s. 185-194
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Tidskriftsartikel (refereegranskat)
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