FPGA-based Bit-Error-Rate Tester for SEU-hardened Optical Links

The next generation of optical links for future High-Energy Physics experiments will require components qualified for use in radiation-hard environments. To cope with radiation induced single-event upsets, the physical layer protocol will include Forward Error Correction (FEC). Bit-Error-Rate (BER) testing is a widely used method to characterize digital transmission systems. In order to measure the BER with and without the proposed FEC, simultaneously on several devices, a multi-channel BER tester has been developed. This paper describes the architecture of the tester, its implementation in a Xilinx Virtex-5 FPGA device and discusses the experimental results

Two years after molecular diagnosis of familial hypercholesterolemia: Majority on cholesterol-lowering treatment but a minority reaches treatment goal

Background: The risk of premature cardiovascular disease in patients with familial hypercholesterolemia (FH) can be profoundly reduced by cholesterol-lowering therapy, and current guidelines for FH advocate ambitious low-density lipoprotein cholesterol (LDL-C) goals. In the present study, we determined whether these goals are reflected in current clinical practice once FH has been diagnosed. Methodology/Principal Findings: In 2008, we sent questionnaires to all subjects (aged 18-65 years) who were molecularly diagnosed with FH in the year 2006 through the screening program in the Netherlands. Of these 1062 subjects, 781 completed the questionnaire (46% males; mean age: 42±12 years; mean LDL-C at molecular diagnosis (baseline): 4.1±1.3 mmol/L). The number of persons that used cholesterol-lowering therapy increased from 397 (51%) at baseline to 636 (81%) after diagnosis. Mean treated LDL-C levels decreased significantly to 3.2±1.1 mmol/L two years after diagnosis. Only 22% achieved the LDL-C target level of ≤2.5 mmol/L. Conclusions/Significance: The proportion of patients using cholesterol-lowering medication was significantly increased after FH diagnosis through

Mechanisms of anti-VEGF therapy-induced kidney injury:current insights and future perspectives in combination with immune checkpoint inhibitors

The formation of new blood vessels is crucial for tumour and metastatic progression. Consequently, targeted therapies directed towards the vascular endothelial growth factor (VEGF) pathway have significantly improved treatment outcomes in several malignancies. These treatment modalities are frequently used in current oncologic practice, as monotherapy, or in combination with other anti-cancer regimens such as immune checkpoint inhibitors (ICIs), to enhance the anti-cancer effects. Despite their proven efficacy, anti-VEGF therapies are also known to cause substantial renal toxicity. Common renal side effects include hypertension, proteinuria, renal dysfunction, thrombotic microangiopathy, and in some cases, renal failure. These adverse effects pose significant challenges in clinical practice, as kidney damage can lead to lower dosing of anti-cancer treatment and compromise quality of life. The mechanisms underlying kidney toxicity associated with anti-VEGF therapies, including in combination with ICIs, are poorly understood. A deeper understanding of these mechanisms is essential for mitigating kidney damage and preserving kidney function during treatment. This review aims to explore the role of VEGF in renal physiology, the incidence of renal toxicities associated with anti-VEGF therapies, and the potential mechanisms driving these toxicities, with particular emphasis on the endothelin, nitric oxide, and prostanoid pathways. Additionally, the review will address the renal effects observed when anti-VEGF therapies are combined with ICIs, as both treatment modalities are independently associated with kidney-related adverse effects, along with the underlying mechanisms involved.</p

COvid MEdicaTion (COMET) study: protocol for a cohort study

Various theories about drugs such as ACE inhibitors or angiotensin II receptor blockers (ARBs) in relation to severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) and clinical outcomes of COVID-19 are circulating in both mainstream media and medical literature. These are based on the fact that ACE2 facilitates SARSCoV-2 cell invasion via binding of a viral spike protein to ACE2. However, the effect of ACE inhibitors, ARBs and other drugs on ACE2 is unclear and all theories are based on conflicting evidence mainly from animal studies. Therefore, clinical evidence is urgently needed. The aim of this study is to investigate the relationship between use of these drugs on clinical outcome of patients with COVID-19. Patients will be included from several hospitals in Europe. Data will be collected in a user-friendly database (Digitalis) on an external server. Analyses will be adjusted for sex, age and presence of cardiovascular disease, hypertension and diabetes. These results will enable more rational choices for randomised controlled trials for preventive and therapeutic strategies in COVID-19

Efficacy and Safety of High Potent P2Y12 Inhibitors Prasugrel and Ticagrelor in Patients With Coronary Heart Disease Treated With Dual Antiplatelet Therapy: A Sex-Specific Systematic Review and Meta-Analysis

Background Sex differences in efficacy and safety of dual antiplatelet therapy remain uncertain because of the underrepresentation of women in cardiovascular trials. The aim of this study was to perform a sex-specific analysis of the pooled efficacy and safety data of clinical trials comparing a high potent P2Y12 inhibitor+aspirin with clopidogrel+aspirin in patients with acute coronary syndrome. Methods and Results A systematic literature search was performed. Randomized clinical trials that compared patients following percutaneous coronary intervention/acute coronary syndrome who were taking high potent P2Y12 inhibitors+aspirin versus clopidogrel+aspirin were selected. Random effects estimates were calculated and relative risks with 95% CIs on efficacy and safety end points were determined per sex. We included 6 randomized clinical trials comparing prasugrel/ticagrelor versus clopidogrel in 43 990 patients (13 030 women), with a median follow-up time of 1.06 years. Women and men had similar relative risk (RR) reduction for major cardiovascular events (women: RR, 0.89 [95% CI, 0.80-1.00; men: RR, 0.84 [95% CI, 0.79-0.91) (P for interaction=0.39). Regarding safety, women and men had similar risk of major bleeding by high-potency dual antip

Trigeminovascular effects of propranolol in men and women, role for sex steroids

OBJECTIVE: Assess whether propranolol modulates the trigeminovascular system in both men and women. METHODS: We investigated the effect of propranolol (80 mg, 90 min after oral administration, corresponding to T (max)) on the increase in dermal blood flow of the forehead skin (innervated by the trigeminal nerve) by capsaicin application (0.6 mg/mL) and electrical stimulation (0.2–1.0 mA) before and after placebo (grapefruit juice) or propranolol (oral solution diluted in grapefruit juice) in a randomized, double‐blind, placebo‐controlled cross‐over study, including healthy males (n = 10) and females on contraceptives (n = 11). Additionally, we compared our results with data from the Dutch IADB.nl prescription database by analyzing the change in triptan use after propranolol prescription in a population similar to our dermal blood flow study subjects (males and females, 20–39 years old). RESULTS: Dermal blood flow responses to capsaicin were significantly attenuated after propranolol, but not after placebo. When stratifying by sex, no significant changes in the capsaicin‐induced dermal blood flow were observed in females after propranolol, whereas they remained significant in males. Dermal blood flow responses to electrical stimulation were not modified in any case. In our prescription database study, after propranolol, a more pronounced decrease in triptan use was observed in male patients than in female patients. INTERPRETATION: Propranolol (80 mg) inhibits capsaicin‐induced increases in dermal blood flow in a sex‐dependent manner. In patients, a more pronounced decrease in triptan use is observed in males when compared with females, suggesting an interaction between propranolol and sex steroids in the modulation of the trigeminovascular system

Efficacy of statins in familial hypercholesterolaemia: a long term cohort study

Objective To determine the efficacy of statin treatment on risk of coronary heart disease in patients with familial hypercholesterolaemia

The interplay between tamoxifen and endoxifen plasma concentrations and coagulation parameters in patients with primary breast cancer

Background: Tamoxifen is an effective treatment for primary breast cancer but increases the risk for venous thromboembolism. Tamoxifen decreases anticoagulant proteins, including antithrombin (AT), protein C (PC) and tissue factor (TF) pathway inhibitor, and enhances thrombin generation (TG). However, the relation between plasma concentrations of both tamoxifen and its active metabolite endoxifen and coagulation remains unknown. Methods: Tamoxifen and endoxifen were measured in 141 patients from the prospective open-label intervention TOTAM-study after 3 months (m) and 6 m of tamoxifen treatment. Levels of AT and PC, the procoagulant TF, and TG parameters were determined at both timepoints if samples were available (n = 53–135 per analysis). Levels of coagulation proteins and TG parameters were correlated and compared between: 1) quartiles of tamoxifen and endoxifen levels, and 2) 3 m and 6 m of treatment. Results: At 3 m, levels of AT, PC, TF and TG parameters were not associated with tamoxifen nor endoxifen levels. At 6 m, median TF levels were lower in patients in the 3rd (56.6 [33] pg/mL), and 4th (50.1 [19] pg/mL) endoxifen quartiles compared to the 1st (lowest) quartile (76 [69] pg/mL) (P=0.027 and P=0.018, respectively), but no differences in anticoagulant proteins or TG parameters were observed. An increase in circulating TF levels (3 m: 46.0 [15] versus 6 m: 54.4 [39] pg/mL, P &lt; 0.001) and TG parameters was observed at the 6 m treatment timepoint, while AT and PC levels remained stable.Conclusions: Our results indicate that higher tamoxifen and endoxifen levels are not correlated with an increased procoagulant state, suggesting tamoxifen dose escalation does not further promote hypercoagulability.</p

Aspirin for the prevention and treatment of pre-eclampsia: A matter of COX-1 and/or COX-2 inhibition?

Since the 1970s, we have known that aspirin can reduce the risk of pre-eclampsia. However, the underlying mechanisms explaining this risk reduction are poorly understood. Both cyclooxygenase (COX)-1- and COX-2-dependent effects might be involved. As a consequence of this knowledge hiatus, the optimal dose and timing of initiation of aspirin therapy are not clear. Here, we review how (COX-1 versus COX-2 inhibition) and when (prevention versus treatment) aspirin therapy may interfere with the mechanisms implicated in the pathogenesis of pre-eclampsia. The available evidence suggests that both COX-1- and COX-2-dependent effects play im