49 research outputs found
A Fatal Case of Ciprofloxacin-induced Fulminant Hepatitis
Fatal hepatotoxicity associated with ciprofloxacin is extremely rare. This is the second fully investigated case of fulminant hepatotoxicity due to ciprofloxacin in a male patient previously ciprofloxacin tolerant. The patient’s medical history included stable Waldenstrom’s macroglobulinaemia, inguinal hernia repair, prostate cancer (radiotherapy in 2006) and idiopathic Parkinson’s disease. Extensive investigation for progressive liver failure confirmed drug-induced liver injury
Analysis of dynamic wireless power transfer systems based on behavioral modeling of mutual inductance
This paper proposes a system-level approach suitable to analyze the performance of a dynamic Wireless Power Transfer System (WPTS) for electric vehicles, accounting for the uncertainty in the vehicle trajectory. The key-point of the approach is the use of an analytical behavioral model that relates mutual inductance between the coil pair to their relative positions along the actual vehicle trajectory. The behavioral model is derived from a limited training data set of simulations, by using a multi-objective genetic programming algorithm, and is validated against experimental data, taken from a real dynamic WPTS. This approach avoids the massive use of computationally expensive 3D finite element simulations, that would be required if this analysis were performed by means of look-up tables. This analytical model is here embedded into a system-level circuital model of the entire WPTS, thus allowing a fast and accurate analysis of the sensitivity of the performance as the actual vehicle trajectory deviates from the nominal one. The system-level analysis is eventually performed to assess the sensitivity of the power and efficiency of the WPTS to the vehicle misalignment from the nominal trajectory during the dynamic charging process
Eurofusion-DEMO Divertor - Cassette Design and Integration
The Eurofusion-DEMO design will complete the Pre Conceptual Design phase (PCD) with a PCD Gate, named G1, scheduled to take place in Q4 2020 that will focus on assessing the feasibility of the plant and its main components prior to entering into the Conceptual Design phase. In the paper first an overview is given of the Eurofusion-DEMO Divertor Assembly including design and interface description, systems and functional requirements, load specification, system classification, manufacturing procedures and cost estimate. Then critical issues are discussed and potential design solutions are proposed, e.g.: - Neutron material damage limits of the different (structural) materials present in the divertor assembly (as CuCrZr, Eurofer) and in the vacuum vessel (AISI 316 L(N)-IG); - Temperature hot spots in parts of the divertor assembly exposed to high nuclear heating and high heat radiation (from the plasma core or the separatrix) causing difficulties for active or passive cooling (e.g. cassette body structure, liner support structures, mechanical supports, divertor toroidal rails); - Arrangement and design of plasma-facing components and liner with pumping slot in the divertor cassette to enable pumping of exhaust gases from the lower port
Divertor of the European DEMO: Engineering and technologies for power exhaust
In a power plant scale fusion reactor, a huge amount of thermal power produced by the fusion reaction and external heating must be exhausted through the narrow area of the divertor targets. The targets must withstand the intense bombardment of the diverted particles where high heat fluxes are generated and erosion takes place on the surface. A considerable amount of volumetric nuclear heating power must also be exhausted. To cope with such an unprecedented power exhaust challenge, a highly efficient cooling capacity is required. Furthermore, the divertor must fulfill other critical functions such as nuclear shielding and channeling (and compression) of exhaust gas for pumping. Assuring the structural integrity of the neutron-irradiated (thus embrittled) components is a crucial prerequisite for a reliable operation over the lifetime. Safety, maintainability, availability, waste and costs are another points of consideration.
In late 2020, the Pre-Conceptual Design activities to develop the divertor of the European demonstration fusion reactor were officially concluded. On this occasion, the baseline design and the key technology options were identified and verified by the project team (EUROfusion Work Package Divertor) based on seven years of R&D efforts and endorsed by Gate Review Panel.
In this paper, an overview of the load specifications, brief descriptions of the design and the highlights of the technology R&D work are presented together with the further work still needed
Klinefelter syndrome: cardiovascular abnormalities and metabolic disorders
Klinefelter syndrome (KS) is one of the most common genetic causes of male infertility. This condition is associated with much comorbidity and with a lower life expectancy. The aim of this review is to explore more in depth cardiovascular and metabolic disorders associated to KS. KS patients have an increased risk of cerebrovascular disease (standardized mortality ratio, SMR, 2.2; 95% confidence interval, CI, 1.6–3.0), but it is not clear whether the cause of the death is of thrombotic or hemorrhagic nature. Cardiovascular congenital anomalies (SMR, 7.3; 95% CI, 2.4–17.1) and the development of thrombosis or leg ulcers (SMR, 7.9; 95% CI, 2.9–17.2) are also more frequent in these subjects. Moreover, cardiovascular abnormalities may be at least partially reversed by testosterone replacement therapy (TRT). KS patients have also an increased probability of endocrine and/or metabolic disease, especially obesity, metabolic syndrome and type 2 diabetes mellitus. The effects of TRT on these abnormalities are not entirely clear
Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study
BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure
Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF Therapy (IMSAT) therapeutic drug monitoring study
Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study
BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure
Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid : community-based randomized clinical trial in Italy and the Netherlands
Background: In 2010 a Cochrane review confirmed that folic acid (FA) supplementation prevents the first- and second-time occurrence of neural tube defects (NTDs). At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital malformations (CMs) or the risk of a specific and selected group of them, namely cardiac defects and oral clefts. Furthermore, the effects on the prevention of prematurity, foetal growth retardation and pre-eclampsia are unclear.Although the most common recommendation is to take 0.4 mg/day, the problem of the most appropriate dose of FA is still open.The aim of this project is to assess the effect a higher dose of peri-conceptional FA supplementation on reducing the occurrence of all CMs. Other aims include the promotion of pre-conceptional counselling, comparing rates of selected CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age, abruptio placentae.Methods/Design: This project is a joint effort by research groups in Italy and the Netherlands. Women of childbearing age, who intend to become pregnant within 12 months are eligible for the studies. Women are randomly assigned to receive 4 mg of FA (treatment in study) or 0.4 mg of FA (referent treatment) daily. Information on pregnancy outcomes are derived from women-and-physician information.We foresee to analyze the data considering all the adverse outcomes of pregnancy taken together in a global end point (e.g.: CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age). A total of about 1,000 pregnancies need to be evaluated to detect an absolute reduction of the frequency of 8%. Since the sample size needed for studying outcomes separately is large, this project also promotes an international prospective meta-analysis.Discussion: The rationale of these randomized clinical trials (RCTs) is the hypothesis that a higher intake of FA is related to a higher risk reduction of NTDs, other CMs and other adverse pregnancy outcomes. Our hope is that these trials will act as catalysers, and lead to other large RCTs studying the effects of this supplementation on CMs and other infant and maternal outcomes.Trial registration: Italian trial: ClinicalTrials.gov Identifier: NCT01244347.Dutch trial: Dutch Trial Register ID: NTR3161