466 research outputs found

    Blind Schnorr Signatures and Signed ElGamal Encryption in the Algebraic Group Model

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    The Schnorr blind signing protocol allows blind issuing of Schnorr signatures, one of the most widely used signatures. Despite its practical relevance, its security analysis is unsatisfactory. The only known security proof is rather informal and in the combination of the generic group model (GGM) and the random oracle model (ROM) assuming that the ``ROS problem\u27\u27 is hard. The situation is similar for (Schnorr-)signed ElGamal encryption, a simple CCA2-secure variant of ElGamal. We analyze the security of these schemes in the algebraic group model (AGM), an idealized model closer to the standard model than the GGM. We first prove tight security of Schnorr signatures from the discrete logarithm assumption (DL) in the AGM+ROM. We then give a rigorous proof for blind Schnorr signatures in the AGM+ROM assuming hardness of the one-more discrete logarithm problem and ROS. As ROS can be solved in sub-exponential time using Wagner\u27s algorithm, we propose a simple modification of the signing protocol, which leaves the signatures unchanged. It is therefore compatible with systems that already use Schnorr signatures, such as blockchain protocols. We show that the security of our modified scheme relies on the hardness of a problem related to ROS that appears much harder. Finally, we give tight reductions, again in the AGM+ROM, of the CCA2 security of signed ElGamal encryption to DDH and signed hashed ElGamal key encapsulation to DL

    Investigating Historical Abuses: An Applied History Perspective on intercountry Adoption in the Netherlands, 1950s-Present

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    This article investigates the phenomenon and practice of intercountry adoption from a historical perspective by using applied history methods. In particular, we employed the method of historicizing current concerns, such as the notion of abuses, and contextualizing them in history. With these methods, we contributed to the Dutch governmental assessment and evaluation of intercountry adoption, indicating that our findings (as laid down in the official report) need to be translated into revised governmental policies. In this paper, we describe how we applied our historicizing methods to intercountry adoption abuses by providing a narrative and genealogy of the topic. We also discuss the pitfalls and merits of conducting historical research into practices that are now considered immoral or unjust, but were long standard practice after intercountry adoption started in the Netherlands. In this way, we also contribute to the ongoing discussion on doing historical research in highly politicized contexts, where the danger of contributing to the ‘blame game’ often lies in wait

    Preparing medical first responders for crises: a systematic literature review of disaster training programs and their effectiveness.

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    BACKGROUND Adequate training and preparation of medical first responders (MFRs) are essential for an optimal performance in highly demanding situations like disasters (e.g., mass accidents, natural catastrophes). The training needs to be as effective as possible, because precise and effective behavior of MFRs under stress is central for ensuring patients' survival and recovery. This systematic review offers an overview of scientifically evaluated training methods used to prepare MFRs for disasters. It identifies different effectiveness indicators and provides an additional analysis of how and to what extent the innovative training technologies virtual (VR) and mixed reality (MR) are included in disaster training research. METHODS The systematic review was conducted according to the PRISMA guidelines and focused specifically on (quasi-)experimental studies published between January 2010 and September 2021. The literature search was conducted via Web of Science and PubMed and led to the inclusion of 55 articles. RESULTS The search identified several types of training, including traditional (e.g., lectures, real-life scenario training) and technology-based training (e.g., computer-based learning, educational videos). Most trainings consisted of more than one method. The effectiveness of the trainings was mainly assessed through pre-post comparisons of knowledge tests or self-reported measures although some studies also used behavioral performance measures (e.g., triage accuracy). While all methods demonstrated effectiveness, the literature indicates that technology-based methods often lead to similar or greater training outcomes than traditional trainings. Currently, few studies systematically evaluated immersive VR and MR training. CONCLUSION To determine the success of a training, proper and scientifically sound evaluation is necessary. Of the effectiveness indicators found, performance assessments in simulated scenarios are closest to the target behavior during real disasters. For valid yet inexpensive evaluations, objectively assessible performance measures, such as accuracy, time, and order of actions could be used. However, performance assessments have not been applied often. Furthermore, we found that technology-based training methods represent a promising approach to train many MFRs repeatedly and efficiently. These technologies offer great potential to supplement or partially replace traditional training. Further research is needed on those methods that have been underrepresented, especially serious gaming, immersive VR, and MR

    Detailed cross-sectional study of 60 superficial femoral artery occlusions: morphological quantitative analysis can lead to a new classification.

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    OBJECTIVE: Current clinical classification of superficial femoral artery (SFA) occlusions as defined by TASC II guidelines is limited to length and calcifications analysis on 2D angiograms, while state-of-the-art cross-sectional imaging like computed tomography angiography (CTA) and magnetic resonance angiography (MRA) provides much more detailed anatomical information than traditional invasive angiography: quantitative morphological analysis of these advanced imaging techniques could therefore be the basis of a refined classification. METHODS AND RESULTS: Forty-six patients (65% men, 68±11.6 years) that underwent lower limb CTA were retrospectively included, totalizing 60 SFA occlusions. Lesions were classified as TASC II stage A in 3% of cases, stage B in 20%, stage C in 2% and stage D in 75%. For each pathological artery, curved multiplanar reconstructions following the occluded SFA course were used to measure the total length and the mean diameter of the occluded segment. Color-coded map provided an accurate estimation of calcifications' volume. Thirty-nine percent of the occlusions were total. Mean occluded segment length was 219±107 mm (range, 14-530 mm); mean occluded segment diameter was 6.1±1.6 mm (range, 3.4-10 mm); mean calcifications' volume in the occluded segment was 1,265±1,893 mm(3) (range, 0-8,815 mm(3)), corresponding to a percentage of 17.4%±20% (range, 0-88.7%). Shrinked occluded occlusions were defined by a mean diameter under 5 mm and heavily calcified occlusions by a mean percentage of calcifications above 4%. Use of these thresholds allowed the distinction of four groups of patients: heavily calcified occlusions with preserved caliber (56%), non-calcified occlusions with preserved caliber (19%), non-calcified occlusions with small caliber (15%) and heavily calcified occlusions with small caliber (10%). CONCLUSIONS: SFA OCCLUSIONS ARE DISPARATE: this simple morphological study points out TASC II classification weaknesses for SFA occlusions, as quantitative cross-sectional imaging analysis with measurement of mean occluded diameter and percentage of calcifications can refine it. This could be particularly useful in the management of TASC II type D lesions, for which new endovascular revascularization techniques are arising, and where a CTA or MRA-based morphological classification could provide support in choosing between them..journal article2014 Aprimporte

    Recanalization Therapies for Large Vessel Occlusion Due to Cervical Artery Dissection: A Cohort Study of the EVA-TRISP Collaboration

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    Background and Purpose: This study aimed to investigate the effect of endovascular treatment (EVT, with or without intravenous thrombolysis [IVT]) versus IVT alone on outcomes in patients with acute ischemic stroke (AIS) and intracranial large vessel occlusion (LVO) attributable to cervical artery dissection (CeAD). Methods: This multinational cohort study was conducted based on prospectively collected data from the EVA-TRISP (EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients) collaboration. Consecutive patients (2015–2019) with AIS-LVO attributable to CeAD treated with EVT and/or IVT were included. Primary outcome measures were (1) favorable 3-month outcome (modified Rankin Scale score 0–2) and (2) complete recanalization (thrombolysis in cerebral infarction scale 2b/3). Odds ratios with 95% confidence intervals (OR [95% CI]) from logistic regression models were calculated (unadjusted, adjusted). Secondary analyses were performed in the patients with LVO in the anterior circulation (LVOant) including propensity score matching. Results: Among 290 patients, 222 (76.6%) had EVT and 68 (23.4%) IVT alone. EVT-treated patients had more severe strokes (National Institutes of Health Stroke Scale score, median [interquartile range]: 14 [10–19] vs. 4 [2–7], Padjusted 0.56 [0.24–1.32]). EVT was associated with higher rates of recanalization (80.5% vs. 40.7%; ORadjusted 8.85 [4.28–18.29]) compared to IVT. All secondary analyses showed higher recanalization rates in the EVT-group, which however never translated into better functional outcome rates compared to the IVT-group. Conclusion: We observed no signal of superiority of EVT over IVT regarding functional outcome in CeAD-patients with AIS and LVO despite higher rates of complete recanalization with EVT. Whether pathophysiological CeAD-characteristics or their younger age might explain this observation deserves further research

    Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

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    Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≄7, valid mRSS at 12±3 months after baseline and ≄1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ≄25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≄10% (53.6% vs 34.4%; p<0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≀22/51) or short disease duration (≀15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≄10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice

    Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

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    Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

    Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

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    Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≄6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

    Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

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    Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction &gt;0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

    Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

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    Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049
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