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Objectives: The aim of this review paper is to summarise surgical options available for repairing iris defects at the iris–lens plane, focusing on suturing techniques, iridodialysis repair, and prosthetic iris devices. Methods: A thorough literature search was conducted using multiple databases, including Medline, PubMed, Web of Science Core Collection, and the Cochrane Library, from inception to February 2024. Relevant studies were screened based on predefined criteria, and primary references cited in selected articles were also reviewed. Results: Various surgical techniques were identified for iris defect repair. Suturing methods such as interrupted full-thickness sutures and the McCannel technique offer solutions for smaller defects, while iridodialysis repair techniques address detachment of the iris from the ciliary body. Prosthetic iris devices, including iris–lens diaphragm devices, endocapsular capsular tension ring-based devices, and customizable artificial iris implants, provide options for larger defects, each with its own advantages and limitations. Conclusions: Successful iris reconstruction requires a personalised approach considering factors like defect size, ocular comorbidities, and patient preference. Surgeons must possess a thorough understanding of available techniques and prosthetic devices to achieve optimal outcomes in terms of both visual function and, nonetheless, cosmetic appearance. [ABSTRACT FROM AUTHOR]

An essential means of collecting more abdominal donor organs is controlled donation after circulatory death (cDCD). The organs are typically preserved during cDCD using the abdominal normothermic regional perfusion (A-NRP) technique to recirculate oxygenated blood flow following cardiac arrest and the withdrawal of life support. One of the challenges of A-NRP is ensuring the correct vascular devices' positionings, specifically extracorporeal membrane oxygenation cannulae and aortic balloons, typically achieved through fluoroscopy with or without contrast agents. Here, we present a case report in which transesophageal echocardiography (TEE) helped the transplant team to effectively procure viable abdominal organs from a cDCD donor in the shortest time frame, as minimizing time is one of the most crucial factors in maintaining organ viability. TEE use leads to a more effective and efficient A-NRP procedure with limited complications. In addition, it allows us to observe the circulation of both the thoracic and part of the abdominal organs using one fast exam. This case is the first report describing TEE as a primary guide and useful tool for DCD donors. However, prospective studies are needed to confirm that TEE could be used as standard practice during all DCD organ retrieval procedures. [ABSTRACT FROM AUTHOR]

Inter-story isolation system (IIS) is increasingly being sought to add floors on top of existing buildings while controlling their base shear forces. One of the main issues with this application is the need to control the drift between the two structural parts and the acceleration of the superstructure, while optimizing the substructure performance. Therefore, this study investigates the use of the IIS as a structural Tuned Mass Damper (TMD), proposing a specific multi-objective optimization approach and providing new design equations for the IIS parameters. Unlike conventional TMD approaches, which focus on the performance of the primary structure (i.e., substructure), the proposed approach aims to consider the overall structural response. The optimal solutions obtained are then compared with the consistent ones currently available in the literature. Finally, time-history analyses of three simple case study structures are performed to validate these optimized solutions. The results demonstrate the potential of the IIS in improving the seismic performance of the substructure, as well as the possibility of limiting the isolation drifts and superstructure accelerations according to specific needs. [ABSTRACT FROM AUTHOR]

We study the effect of Gaussian perturbations on a hyperbolic partial differential equation with double characteristics in two spatial dimensions. The coefficients of our partial differential operator depend polynomially on the space variables, while the noise is additive, white in time and coloured in space. We provide a sufficient condition on the spectral measure of the covariance functional describing the noise that allows for the existence of a random field solution for the resulting stochastic partial differential equation. Our approach is based on explicit computations for the fundamental solution of the partial differential operator and its Fourier transform. [ABSTRACT FROM AUTHOR]

At the 6-months time point, the standard anticoagulation course for most patients, 5.3% (0.0 to 11.2%) of patients with CAT and 1.3% (0.3 to 2.3%) without CAT had experienced a major bleeding event. The corresponding incidence rates were 6.6 (95% CI 2.1 to 15.4) and 1.4 (95% CI 0.6 to 2.79) per 100 patient years (RR 4.6; 95% CI 1.2 to 15.4; I p i = 0.002); over a cumulative follow-up of 75.9 and 634.1 patient years, respectively. At the 6-months time point, the standard anticoagulation course for most patients, 5.5% (0.0 to 11.6%) of patients with CAT versus 1.8% (0.6 to 3.0%) without CAT had experienced a recurrent event. This observation matches with data from a classic follow-up study with VKA, in which patients with cancer had a more than doubled 12-month incidence of major bleeding during anticoagulant treatment than patients free of malignancy [[1]]. [Extracted from the article]

Venous thromboembolism (VTE) is a major cause of death in the world. After the acute-phase treatment, the optimal duration of anticoagulation is still debatable. The latest guidelines suggest maintaining long-term anticoagulation in patients with cancer-associated thrombosis (CAT) or with unprovoked VTE and a low bleeding risk. Methods: The MAC Project is an ongoing prospective-cohort, multi-center, observational study in Italy. The project aims to collect real-life clinical information in unselected patients given oral anticoagulants for VTE over a 5-year follow-up period. There were no exclusion criteria, except for life expectancy <6 months and refusal to sign the informed consent form or to attend the planned follow-up visit. All patients were followed-up prospectively with clinical controls scheduled at 3, 6, and 12 months after the index event, and then annually for up to 5 years. The primary efficacy and safety outcomes were symptomatic recurrent VTE and major bleeding. Results: We analyzed 450 consecutive patients treated with rivaroxaban and referred them to the MAC Project database for unprovoked or recurrent VTE. Of these, 267 (55%) were unprovoked VTE, and 377 (87%) were symptomatic. We followed up with the patients for a mean of 22 months (Q1 10.7; Q3 37.4 months). Recurrent VTE occurred in 12 patients on rivaroxaban treatment (IR 1.7 per 100 person-years). Males had more recurrence than women. During the follow-up period, we recorded 13 (2.9%) major bleeding, 12 (2.7%) clinically relevant non-major bleeding, 8 minor bleeding, and no fatal bleeding events. Overall, bleeding events occurred in 33 (7.3%) patients, most occurring within the first 2 years of treatment. In addition, we observed a statistically significant higher incidence of bleeding in patients with a baseline HAS-BLED score of 3 to 4 compared with those with a score of 0 to 2, with most events occurring during the first 3 months of treatment (RR 5.9). Discussion: Rivaroxaban appears to be safe and effective for the long-term treatment of patients with recurrent or unprovoked VTE. Our results match previously published data, and we are confident that the continuation of the follow-up for up to 5 years will confirm these outcomes. [ABSTRACT FROM AUTHOR]

This paper studies a new nonconvex optimization problem aimed at recovering high-dimensional covariance matrices with a low rank plus sparse structure. The objective is composed of a smooth nonconvex loss and a nonsmooth composite penalty. A number of structural analytic properties of the new heuristics are presented and proven, thus providing the necessary framework for further investigating the statistical applications. In particular, the first and the second derivative of the smooth loss are obtained, its local convexity range is derived, and the Lipschitzianity of its gradient is shown. This opens the path to solve the described problem via a proximal gradient algorithm. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to address the safety and effectiveness of a second continuous-wave transscleral cyclophotocoagulation (CW-TSCPC) treatment by comparing its outcome against a first CW-TSCPC treatment in the same patients with refractory glaucoma. Methods: Twenty-one eyes with either primary or secondary glaucoma received a second CW-TSCPC laser session ≥ 3 months after the first treatment. Intraocular pressure (IOP), best-corrected visual acuity (BCVA), and number of topical or oral ophthalmic pressure-reducing medications were registered at every time point up to the last follow-up at 3 months. A complete slit-lamp examination was conducted to record for complications or other abnormal ocular findings. Success was defined as IOP between 6 and 21 mmHg and > 20% reduction in IOP with or without anti-glaucoma medications. Results: At 3 months follow-up of the first CW-TSCPC treatment, a 24.8% decrease in IOP was observed, whereas a 45.6% IOP decrease was observed 3 months post the second CW-TSCPC treatment. Visual acuity did not decrease, and no major complications were observed post either treatment within the follow-up period. Time to failure was 79.5 ± 24.6 and 77.1 ± 29.4, respectively (P = 0.955). No serious complications were observed. Conclusion: A second CW-TSCPC treatment proved to be a safe and effective treatment option when the first CW-TSCPC treatment was insufficient in maintaining the desired IOP level for a prolonged time (mean time between both sessions 6.4 ± 8.0 months). [ABSTRACT FROM AUTHOR]

We perturb with an additive noise the Hamiltonian system associated to a cubic anharmonic oscillator. This gives rise to a system of stochastic differential equations with quadratic drift and degenerate diffusion matrix. Firstly, we show that such systems possess explosive solutions for certain initial conditions. Then, we carry a small noise expansion's analysis of the stochastic system which is assumed to start from initial conditions that guarantee the existence of a periodic solution for the unperturbed equation. We then investigate the probabilistic properties of the sequence of coefficients which turn out to be the unique strong solutions of stochastic perturbations of the well-known Lamé's equation. We also obtain explicit expressions of these in terms of Jacobi elliptic functions. Furthermore, we prove, in the case of Brownian noise, a lower bound for the probability that the truncated expansion stays close to the solution of the deterministic problem. Lastly, when the noise is bounded, we provide conditions for the almost sure convergence of the global expansion. [ABSTRACT FROM AUTHOR]

In Gray et al. [A stochastic differential equation SIS epidemic model, SIAM J. Appl. Math. 71 (3) (2011) 876–902] a susceptible‐infected‐susceptible (SIS) stochastic differential equation (SDE), obtained via a suitable random perturbation of the disease transmission coefficient in the classic SIS model, has been studied. Such random perturbation enters via an informal manipulation of stochastic differentials and leads to an Itô's‐type SDE. The authors identify a stochastic reproduction number, which differs from the standard one for the presence of those additional parameters that describe the employed random perturbation, and show that, similarly to the deterministic case, the stochastic reproduction number rules the asymptotic behavior of the solution. Aiming to make that random perturbation rigorous, we suggest an alternative approach based on a Wong–Zakai approximation argument thus arriving at a different stochastic model corresponding to the Stratonovich version of the Itô equation analyzed in Gray et al. Rather surprisingly, the asymptotic behavior of this alternative model turns out to be governed by the same reproduction number as the deterministic SIS equation. In other words, the random perturbation does not modify the threshold for extinction and persistence of the disease. [ABSTRACT FROM AUTHOR]

Purpose. The aim of this study was to compare effectiveness and safety of MicroPulse transscleral laser therapy (MP-TLT) using the original MicroPulse P3® device and continuous-wave transscleral cyclophotocoagulation (CW-TSCPC) using the G-Probe® device in glaucoma. Methods. Spherical equivalent, intraocular pressure (IOP), best-corrected visual acuity (BCVA), and number of topical or oral ophthalmic pressure-reducing medications were registered at every time point, up to the last follow-up at 12 months. A complete slit-lamp examination was conducted to record the following complications: corneal edema, persistent ocular hypotony (IOP ≤5 mmHg) on two consecutive follow-up visits, choroidal detachment, phthisis bulbi, sympathetic ophthalmia, cystoid macular edema, or other abnormal ocular findings. Success was defined as IOP between 6 and 21 mmHg and >20% reduction in IOP with or without antiglaucoma medications. Results. 47 eyes underwent MP-TLT and 150 CW-TSCPC. At 12 months, success was achieved in 88.6% in the CW-TSCPC group and 87.5% in the MP-TLT group (p = 0.883). In the CW-TSCPC group, eyes achieved a 42.4% IOP reduction (from 28.3 ± 12.3 mmHg to 15.3 ± 6.0 mmHg) and a 31.1% reduction (from 22.0 ± 7.2 mmHg to 15.7 ± 4.8 mmHg) in the MP-TLT group. Visual acuity remained primarily unaltered in both groups. Conclusion. MP-TLT was as effective in lowering IOP as CW-TSCPC and achieved comparable success. Additionally, MP-TLT demonstrated consistent and effective outcomes at every time point. The improved safety profile of MP-TLT allows the therapeutic spectrum to be broadened, granting ophthalmologists' treatment of glaucoma in earlier stages of glaucoma than those typically treated with CW-TSCPC, i.e., early to moderate and to patients with good central-vision. [ABSTRACT FROM AUTHOR]

Inter-storey seismic isolation is increasingly gaining attention. One of the main related issues is the need to limit the relative displacement between substructure and superstructure, while maintaining a good seismic performance of the superstructure. As shown in some studies, fluid viscous dampers (FVDs) mounted in isolation systems are effective in reducing isolator deflection but can be harmful by amplifying inter-storey drifts and floor accelerations. Additionally, the effectiveness of FVDs for inter-storey applications was investigated only recently, and specific approaches for their optimisation and performance evaluation are missing. Therefore, this paper proposes a method for the optimal multi-objective design of FVDs, based on the definition of appropriate surrogate response models, which allows for rationally comparing the FVD effects for a wide range of dampers and structures. In particular, the optimal FVD parameters are provided in a dimensionless form, so that they can be predicted by design equations of general validity within the range of the structures analysed. This method is applied to a stock of regular structures with various vibration periods of superstructure, isolation and substructure, examining a linear and a non-linear isolation system and a set of natural records, in order to comprehensively assess the effects of FVDs and their non-linearity on the seismic performance of these structures. Finally, prediction models of optimal FVD parameters are provided based on the results obtained and are applied to three case studies as an example. [ABSTRACT FROM AUTHOR]

In this paper, we put forward a new model to compute the loss distribution of an automobile insurance company's portfolio evolving by a bonus–malus system. We allow for a continuous evolution of the demographic-economic system based on a migration's rule which is refreshed in discrete time, i.e., at the monitoring times. Therefore, the migration's probabilities are discretely updated through a technique based on the combinatorial distributions of claims' arrival in the rating classes. This technique is hierarchical copula-based, a natural tool permitting us to represent the co-movement between claims' arrivals and distorted due to the formalization of an arrival policy of claims, that restricts the set of combinatorial distributions to those representing the most probable scenarios, therefore distorting the loss function. At every monitoring date, the copula-based model computes the migration's probabilities and the loss function which accommodates for a discrete-time dynamic of the claims' reserving and the capital requirements. An empirical application, the evaluation of the claims' reserving and the capital requirements for different kinds of hierarchies are analyzed, with real data originating with the General Insurance Association of Singapore. [ABSTRACT FROM AUTHOR]

We link a general method for modeling random phenomena using systems of stochastic differential equations (SDEs) to the class of affine SDEs. This general construction emphasizes the central role of the Duffie–Kan system [Duffie and Kan, A yield-factor model of interest rates, Math. Finance 6 (1996) 379–406] as a model for first-order approximations of a wide class of nonlinear systems perturbed by noise. We also specialize to a two-dimensional framework and propose a direct proof of the Duffie–Kan theorem which does not passes through the comparison with an auxiliary process. Our proof produces a scheme to obtain an explicit representation of the solution once the one-dimensional square root process is assigned. [ABSTRACT FROM AUTHOR]

Despite thromboprophylaxis, patients with coronavirus disease 2019 (COVID‐19) exhibit hypercoagulability and higher venous thromboembolic risk, although its real incidence is still unknown. The aim of this study was to evaluate the incidence of venous thromboembolism (VTE) in patients with COVID‐19 admitted to both intensive care units (ICUs) and medical wards (MWs). Consecutive patients admitted for COVID‐19 to the MW and the ICU at Padua University Hospital, all receiving thromboprophylaxis, underwent systematic ultrasonography of the internal jugular, and the upper and lower limbs veins every 7 days (± 1 day) after the admission; and, if negative, once‐weekly until discharge or death. In case of suspected pulmonary embolism, a multidetector computed tomographic angiography was performed. The primary outcome was the proportion of any deep‐vein thrombosis (DVT) and symptomatic pulmonary embolism in both groups. An extended blood coagulative test was performed as well. From March 4 to April 30, 2020, a total of 85 patients were investigated, 44 (52%) in MWs and 41 (48%) in the ICU. Despite thromboprophylaxis, VTE occurred in 12 patients in the MWs (27.3%) and 31 patients in the ICU (75.6%) with an odds ratio of 9.3 (95% confidence interval (CI) 3.5–24.5; P < 0.001). Multiple‐site DVT occurred in 55.6% of patients (95% CI 39.6–70.5). Increased D‐dimer levels significantly correlated with VTE (P = 0.001) and death (P = 0.015). Summarizing, patients with COVID‐19 admitted to the MW or ICU showed a high frequency of venous thromboembolism, despite standard‐dose or high‐dose thromboprophylaxis. Whether thrombosis, particularly asymptomatic events, may play a role in the morbidity and mortality of patients with COVID‐19 remain to be clarified. [ABSTRACT FROM AUTHOR]

BACKGROUND The effect of chronic use of renin–angiotensin–aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension. We aimed to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19-related outcomes in hypertensive patients. METHODS A single-center study was conducted on 133 consecutive hypertensive subjects presenting to the emergency department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9 and 31 March 2020. RESULTS All patients were grouped according to their chronic antihypertensive medications (ACEIs, N = 40; ARBs, N = 42; not on RAAS inhibitors, N = 51). There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy, and need for noninvasive ventilation. Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared with the non-RAAS population (odds ratio (OR) 0.25, confidence interval (CI) 95% 0.09–0.66, P = 0.006). Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI 95% 0.17–1.83, P = 0.341). CONCLUSIONS Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients. Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID-19-related morbidity and mortality. [ABSTRACT FROM AUTHOR]

Aims To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. Methods and results We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 (<6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%). Conclusion Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE. [ABSTRACT FROM AUTHOR]

Inspired by the paper Greenhalgh et al. (Appl Math Comput 276:218–238, 2016), we investigate a class of two-dimensional stochastic differential equations related to susceptible–infected–susceptible epidemic models with demographic stochasticity. While preserving the key features of the model considered in Greenhalgh et al. (2016), where an ad hoc approach has been utilized to prove existence, uniqueness and non-explosivity of the solution, we consider an encompassing family of models described by a stochastic differential equation with random and Hölder continuous coefficients. We prove the existence of a unique strong solution by means of a Cauchy–Euler–Peano approximation scheme which is shown to converge in the proper topologies to the unique solution. [ABSTRACT FROM AUTHOR]

The aim of the paper is to discuss the important role of the dependence structure in risk management. Therefore, we focus on credit-risk and propose an innovative model to value the credit risk of a portfolio. This new approach (HYC for short) is based on a hierarchical hybrid copula and involves a clusterization of the portfolio in several risk's classes. The HYC model is classified as hybrid because the computation of the loss cdf depends on the class's cardinality: for large groups one is justified to apply a limiting approach, while for small ones one applies a procedure preserving the granularity of the group itself. In order to appreciate the impact of the dependence structure in credit-risk evaluation, a VaR analysis based on the HYC loss function is here compared to the CreditMetrics approach in an in-sample exercise and to the empirical VaR in an out-of sample exercise aimed to test the forecasting effectiveness of the model. This comparison allows us to appreciate over/under-valuation of the capital detained from the financial institution. Moreover, the impact of an enlargement of the dependence structure is discussed with respect to the systemic/contagious effects in the context of a portfolio optimisation with constraint on a sub-portfolio's risk. [ABSTRACT FROM AUTHOR]

Despite the availability of updated guidelines for the diagnosis and treatment of venous thromboembolism (VTE), the management of this disorder in clinical practice is often not standardized, given the different degree of compliance with official recommendations by the various involved specialists. The aim of this consensus paper, as a result of a board of experts in thromboembolism, is to define strategies to improve the quality of patients' care and the efficiency of healthcare resources utilization, by means of: (a) analysis of the guidelines for diagnosis and treatment of VTE; (b) analysis of diagnostic and therapeutic algorithms currently used in clinical practice by different specialists; (c) agreement on a common algorithm for diagnosis and treatment of VTE in different clinical settings; (d) definition of the possible role of the new oral anticoagulant agents (NOAC), such as rivaroxaban, based on their potential benefits for both acute and chronic therapy. The so-called "single drug approach" (as opposed to the traditional heparin/VKA combination), which can be adopted with these drugs, makes anticoagulation more convenient for both patients and healthcare providers, without the need for a close monitoring of the hemocoagulative status, and with a concomitant reduction of length of hospitalization and treatment costs. Among NOACs, in this paper we focused on rivaroxaban only because it was the unique available NOAC in Italy for the treatment of VTE at the time the manuscript was written. Concerning rivaroxaban, the results of two phase III, randomized and controlled trials confirm the non-inferiority of this drug compared to standard therapy (enoxaparin/warfarin) for the treatment of patients with pulmonary embolism (EINSTEIN PE Study) or deep vein thrombosis (EINSTEIN DVT Study) in terms of both efficacy and safety, supporting its use as an effective therapeutic option for these disorders. [ABSTRACT FROM AUTHOR]

Clinical Differences between COVID-19 and a COVID-like Syndrome. Reference 1 Di Micco P., Camporese G., Russo V., Cardillo G., Imbalzano E., Tufano A., Bernardi E., Fontanella A. Clinical Differences between COVID-19 and a COVID-Like Syndrome. Table 1 Clinical characteristics of patients with COVID-19-like syndrome and typical COVID-19. [Extracted from the article]

Objective: Emergency physicians frequently deal with patients on vitamin K antagonists (VKAs) suffering major bleeding events, and rapid reversal of anticoagulation in this setting is of paramount importance. In Italy, given the absence of specific national guidelines, local policies are likely to differ, possibly impacting on clinical outcomes. We decided to perform a telephone survey among Italian emergency physicians to evaluate management strategies for VKAs reversal in patients with major bleeding. Methods: We conducted a computer-assisted, 10-minute telephone survey of 15 questions, focusing on the local prevalence, assessment, and management strategies of major and intracranial hemorrhage (ICH) occurring in patients on VKAs. We planned to interview a sample of 320 Italian emergency physicians. Institutions from all geographic areas of Italy were to participate in the survey. Results: Of the 320 physicians contacted, 150 (47%) completed the survey, 95% being employed in public hospitals. Focusing on ICH, only 29% of the responders stated they would reverse anticoagulation irrespective of the international normalized ratio value, and only 27% would use prothrombin-complex concentrate as first-line agent. In patients needing urgent neurosurgical operation, less than 50% would administer prothrombin-complex concentrate before surgery. Conclusion: The average knowledge of management strategies for reversal of anticoagulation displayed by Italian emergency physicians appears to be unsatisfactory. The need for an extensive educational program and for the implementation of specific guidelines, possibly endorsed by Scientific Societies, cannot be underemphasized. [ABSTRACT FROM AUTHOR]

Patients with unprovoked venous thromboembolism (VTE) may harbor occult cancer. Whether an extensive diagnostic work-up for cancer has additional value over a more limited screening for detection of underlying malignancy in these patients is controversial. We performed a randomized multicenter trial to assess if in patients with unprovoked VTE, a computed tomography (CT)-based diagnostic strategy including thoracic, abdominal, and pelvic CT in combination with fecal occult blood test yields a higher cancer detection rate than a nonstandardized testing approach based on physicians' clinical judgment and patients' preferences. Cancer-free patients were followed up for up to 24 months. Of the 195 consecutive patients with unprovoked VTE who were eligible for this investigation, an occult cancer was identified in 10 of the 98 patients (10.2%) randomized to the CT-based strategy, and in 8 of the 97 (8.2%) allocated to the personalized strategy (absolute difference, 2.0%; 95% confidence interval, -7.2-11.1; p = 0.81). During follow-up, cancer was identified in an additional 2 patients in each group. Overall, 7 (7.1%) patients of the CT-based strategy died, as compared with 11 (11.3%) of the personalized strategy, with 2 and 4, respectively, due to cancer. In conclusion, a CT-based strategy in combination with fecal occult blood test does not provide a clinically significant benefit over more limited cancer screening for detecting occult cancer in patients with unprovoked VTE. (ClinicalTrials.gov number, NCT00361647). [ABSTRACT FROM AUTHOR]

In this paper, we propose a novel approach for the computation of the probability distribution of a counting variable linked to a multivariate hierarchical Archimedean copula function. The hierarchy has a twofold impact: it acts on the aggregation step but also it determines the arrival policy of the random event. The novelty of this work is to introduce this policy, formalized as an arrival matrix, i.e., a random matrix of dependent 0-1 random variables, into the model. This arrival matrix represents the set of distorted (by the policy itself) combinatorial distributions of the event, i.e., of the most probable scenarios. To this distorted version of the approach [see Ref. 7 and Ref. 27], we are now able to apply a pure hierarchical Archimedean dependence structure among variables. As an empirical application, we study the problem of evaluating the probability distribution of losses related to the default of various type of counterparts in a structured portfolio exposed to the credit risk of a selected set among the major banks of European area and to the correlations among these risks. [ABSTRACT FROM AUTHOR]

We study a class of third-order hyperbolic operators P in G = {(t, x): 0 ≤ t ≤ T, x ∈ U ⋐ ℝn} with triple characteristics at ρ = (0, x0, ξ), ξ ∈ ℝn ∖{0}. We consider the case when the fundamental matrix of the principal symbol of P at ρ has a couple of non-vanishing real eigenvalues. Such operators are called effectively hyperbolic. Ivrii introduced the conjecture that every effectively hyperbolic operator is strongly hyperbolic, that is the Cauchy problem for P + Q is locally well posed for any lower order terms Q. This conjecture has been solved for operators having at most double characteristics and for operators with triple characteristics in the case when the principal symbol admits a factorization. A strongly hyperbolic operator in G could have triple characteristics in G only for t = 0 or for t = T. We prove that the operators in our class are strongly hyperbolic if T is small enough. Our proof is based on energy estimates with a loss of regularity. [ABSTRACT FROM AUTHOR]

We propose a model for the computation of the loss probability distribution allowing to take into account the not-exchangeable behavior of a portfolio clustered into several classes of homogeneous loans. These classes are classified as `large' or `small' depending on their cardinality. The hierarchical hybrid copula-based model (HHC for short) follows the idea of the clusterized homogeneous copula-based approach (CHC) and its limiting version or the limiting clusterized copula-based model (LCC) proposed in our earlier work. This model allows us to recover a possible risk hierarchy. We suggest an algorithm to compute the HHC loss distribution and we compare this cdf with that computed through the CHC and LCC approaches (in the Gaussian and Archimedean limit) and also with the pure limiting approaches which are commonly used for high-dimensional problems. We study the scalability of the algorithm. [ABSTRACT FROM AUTHOR]

In this paper we prove a well posed and an ill posed result in the Gevrey category for a simple model hyperbolic operator with triple characteristics, when the principal symbol cannot be smoothly factorized, and whose propagation cone is not transversal to the triple characteristic manifold, thus confirming the conjecture that the Ivrii-Petkov condition is not sufficient for the C∞ well posedness unless the propagation cone is transversal to the characteristic manifold, albeit for a limited class of operators. Moreover we are able not only to disprove C∞ well posedness, but we can actually estimate the precise Gevrey threshold where well posedness will cease to hold. [ABSTRACT FROM AUTHOR]

We study the C ∞ well-posedness of the Cauchy problem for a class of hyperbolic second order operators with double characteristics in presence of geometric transitions. [ABSTRACT FROM PUBLISHER]

Siniscalchi A, Cucchetti A, Miklosova Z, Lauro A, Zanoni A, Spedicato S, Bernardi E, Aurini L, Pinna AD, Faenza S. Post-reperfusion syndrome during isolated intestinal transplantation: outcome and predictors. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01530.x © 2011 John Wiley & Sons A/S. Abstract: Background: Post-reperfusion syndrome (PRS) during isolated intestinal transplantation (ITx) is characterized by decreased systemic blood pressure, systemic vascular resistance, and cardiac output and by a moderate increased pulmonary arterial pressure. We hypothesize that the more severe PRS causes a poorer long-term outcome. The primary aim of this study was to determine the independent clinical predictors of intra-operative PRS, as well as to investigate the link between the severity of PRS and the intra-operative profiles and to examine the post-operative complications and their relationship with transplant outcome. Methods: This observational study was conducted on 27 patients undergoing isolated ITx in a single adult liver and multivisceral transplantation center. PRS was considered when the mean arterial blood pressure was 30% lower than the pre-unclamping value and lasted for at least one min within 10 min after unclamping. Results and conclusions: The main results of this study can be summarized in two findings: in patients undergoing ITx, the duration of cold ischemia and the pre-operative glomerular filtration rate were independent predictors of PRS and the occurrence of intra-operative PRS was associated with significantly more frequent post-operative renal failure and early post-operative death. [ABSTRACT FROM AUTHOR]

For hyperbolic differential operators P with double characteristics we study the relations between the maximal Gevrey index for the strong Gevrey well-posedness and the Hamilton map and flow of the associated principal symbol p. If the Hamilton map admits a Jordan block of size 4 on the double characteristic manifold denoted by Σ and by assuming that the Hamilton flow does not approach Σ tangentially, we proved earlier that the Cauchy problem for P is well-posed in the Gevrey class 1 ≤ s < 4 for any lower order term. In the present paper, we remove this restriction on the Hamilton flow and establish that the Cauchy problem for P is well-posed in the Gevrey class 1 ≤ s < 3 for any lower order term and we check that the Gevrey index 3 is optimal. Combining this with results already proved for the other cases, we conclude that the Hamilton map and flow completely characterizes the threshold for the strong Gevrey well-posedness and vice versa. [ABSTRACT FROM AUTHOR]

We propose an algorithm for the computation of the volume of a multivariate copula function (and the probability distribution of the counting variable linked to this multidimensional copula function), which is very complex for large dimensions. As is common practice for large dimensional problem, we restrict ourselves to positive orthant dependence and we construct a Hierarchical copula which describes the joint distribution of random variables accounting for dependence among them. This approach approximates a multivariate distribution function of heterogenous variables with a distribution of a fixed number of homogenous clusters, organized through a semi-unsupervised clustering method. These clusters, representing the second-level sectors of hierarchical copula function, are characterized by an into-sector dependence parameter determined by a method which is very similar to the Diversity Score method. The algorithm, implemented in MatLab™ code, is particularly efficient allowing us to treat cases with a large number of variables, as can be seen in our scalability analysis. As an application, we study the problem of valuing the risk exposure of an insurance company, given the marginals i.e. the risks of each policy. [ABSTRACT FROM AUTHOR]

The article discusses the diagnosis of deep vein thrombosis (DVT), comparing the effectiveness of two diagnostic strategies used with symptomatic outpatients with DVT in their lower extremities. The two strategies both use ultrasonography, but one investigates proximal veins, called serial 2-point ultrasonography plus D-dimer testing, while the other investigates the entire deep-vein system, called whole-leg color-coded Doppler ultrasonography. Whole-leg ultrasonography is considered the better approach, the article indicates, yet requires more skilled operators and tends to only be available during working hours. Also discussed is the need to repeat the 2-point technique within one week of the original test.

Background: Knee arthroscopy, the most common orthopedic operation worldwide, carries a definite risk for deep venous thrombosis; however, postsurgical thromboprophylaxis is not routinely recommended.Objective: To evaluate whether low-molecular-weight heparin (LMWH) better prevents deep venous thrombosis and does not cause more complications than graduated compression stockings in adults having knee arthroscopy.Design: Assessor-blind, randomized, controlled trial.Setting: The Department of Knee Surgery, Abano Terme Clinic, Abano Terme (knee surgery, random assignment, and bleeding event survey), and the Unit of Angiology, University Hospital of Padua, Padua (efficacy outcomes evaluation, follow-up, data management, and analysis), Italy.Patients: 1761 consecutive patients undergoing knee arthroscopy between March 2002 and January 2006.Intervention: Patients were randomly assigned to wear full-length graduated compression stocking for 7 days (660 patients) or to receive a once-daily subcutaneous injection of LMWH (nadroparin, 3800 anti-Xa IU) for 7 days (657 patients) or 14 days (444 patients). The data and safety monitoring board prematurely stopped the 14-day heparin group after the second interim analysis.Measurements: Combined incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality (primary efficacy end point) and combined incidence of major and clinically relevant bleeding events (primary safety end point). All patients had bilateral whole-leg ultrasonography at the end of the allocated prophylactic regimen or earlier if indicated. All patients with normal findings were followed for 3 months, and none was lost to follow-up.Results: The 3-month cumulative incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality was 3.2% (21 of 660 patients) in the stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute difference, 2.3 percentage points [95% CI, 0.7 to 4.0 percentage points]; P = 0.005), and 0.9% (4 of 444 patients) in the prematurely stopped 14-day LMWH group. The cumulative incidence of major or clinically relevant bleeding events was 0.3% (2 of 660 patients) in the stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute difference, -0.6 percentage point [CI, -1.5 to 0.2 percentage points]), and 0.5% (2 of 444 patients) in the 14-day LMWH group.Limitations: The study was not double-blind or double-dummy. Almost half of the events making up the composite outcome measure were distal deep venous thromboses. Stockings were used instead of placebo because of local prophylaxis policies.Conclusion: In patients undergoing knee arthroscopy, prophylactic LMWH for 1 week reduced a composite end point of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality more than did graduated compression stockings. [ABSTRACT FROM AUTHOR]

Background: Knee arthroscopy, the most common orthopedic operation worldwide, carries a definite risk for deep venous thrombosis; however, postsurgical thromboprophylaxis is not routinely recommended. Objective: To evaluate whether low-molecular-weight heparin (LMWH) better prevents deep venous thrombosis and does not cause more complications than graduated compression stockings in adults having knee arthroscopy. Design: Assessor-blind, randomized, controlled trial. Setting: The Department of Knee Surgery, Abano Terme Clinic, Abano Terme (knee surgery, random assignment, and bleeding event survey), and the Unit of Angiology, University Hospital of Padua, Padua (efficacy outcomes evaluation, follow-up, data management, and analysis), Italy. Patients: 1761 consecutive patients undergoing knee arthroscopy between March 2002 and January 2006. Intervention: Patients were randomly assigned to wear full-length graduated compression stocking for 7 days (660 patients) or to receive a once-daily subcutaneous injection of LMWH (nadroparin, 3800 anti-Xa IU) for 7 days (657 patients) or 14 days (444 patients). The data and safety monitoring board prematurely stopped the 14-day heparin group after the second interim analysis. Measurements: Combined incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality (primary efficacy end point) and combined incidence of major and clinically relevant bleeding events (primary safety end point). All patients had bilateral whole-leg ultrasonography at the end of the allocated prophylactic regimen or earlier if indicated. All patients with normal findings were followed for 3 months, and none was lost to follow-up. Results: The 3-month cumulative incidence of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality was 3.2% (21 of 660 patients) in the stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute difference, 2.3 percentage points [95% CI, 0.7 to 4.0 percentage points]; P = 0.005), and 0.9% (4 of 444 patients) in the prematurely stopped 14-day LMWH group. The cumulative incidence of major or clinically relevant bleeding events was 0.3% (2 of 660 patients) in the stockings group, 0.9% (6 of 657 patients) in the 7-day LMWH group (absolute difference, -0.6 percentage point [CI, -1.5 to 0.2 percentage points]), and 0.5% (2 of 444 patients) in the 14-day LMWH group. Limitations: The study was not double-blind or double-dummy. Almost half of the events making up the composite outcome measure were distal deep venous thromboses. Stockings were used instead of placebo because of local prophylaxis policies. Conclusion: In patients undergoing knee arthroscopy, prophylactic LMWH for 1 week reduced a composite end point of asymptomatic proximal deep venous thrombosis, symptomatic venous thromboembolism, and all-cause mortality more than did graduated compression stockings. [ABSTRACT FROM AUTHOR]

In this paper, we prove that for non-effectively hyperbolic operators with smooth double characteristics exhibiting a Jordan block of size 4 on the double manifold, the Cauchy problem is well-posed in the Gevrey 5 class, beyond the generic Gevrey class 2 (see, e.g., [5]). Moreover, we show that this value is optimal, due to certain geometric constraints on the Hamiltonian flow of the principal symbol. These results, together with results already proved, give a complete picture of the well-posedness of the Cauchy problem around hyperbolic double characteristics. [ABSTRACT FROM AUTHOR]

In this paper we prove a well-posedness result for the Cauchy problem. We study a class of first order hyperbolic differential [2] operators of rank zero on an involutive submanifold of T* R n+1-{0} and prove that under suitable assumptions on the symmetrizability of the lifting of the principal symbol to a natural blow up of the “singular part” of the characteristic set, the operator is strongly hyperbolic. [ABSTRACT FROM AUTHOR]

Background: Because only limited evidence suggests that elastic stockings prevent the post-thrombotic syndrome in patients with symptomatic deep venous thrombosis (DVT), these stockings are not widely used.Objective: To evaluate the efficacy of compression elastic stockings for prevention of the post-thrombotic syndrome in patients with proximal DVT.Design: Randomized, controlled clinical trial.Setting: University hospital.Patients: 180 consecutive patients with a first episode of symptomatic proximal DVT who received conventional anticoagulant treatment.Interventions: Before discharge, patients were randomly assigned to wear or not wear below-knee compression elastic stockings (30 to 40 mm Hg at the ankle) for 2 years. Follow-up was performed for up to 5 years.Measurements: The presence and severity of the post-thrombotic syndrome were scored by using a standardized scale.Results: Post-thrombotic sequelae developed in 44 of 90 controls (severe in 10) and in 23 of 90 patients wearing elastic stockings (severe in 3). All but 1 event developed in the first 2 years. The cumulative incidence of the post-thrombotic syndrome in the control group versus the elastic stockings group was 40.0% (95% CI, 29.9% to 50.1%) versus 21.1% (CI, 12.7% to 29.5%) after 6 months, 46.7% (CI, 36.4% to 57.0%) versus 22.2% (CI, 13.8% to 30.7%) after 1 year, and 49.1% (CI, 38.7% to 59.4%) versus 24.5% (CI, 15.6% to 33.4%) after 2 years. After adjustment for baseline characteristics, the hazard ratio for the post-thrombotic syndrome in the elastic stockings group compared with controls was 0.49 (CI, 0.29 to 0.84; P = 0.011).Limitations: This study lacked a double-blind design.Conclusions: Post-thrombotic sequelae develop in almost half of patients with proximal DVT. Below-knee compression elastic stockings reduce this rate by approximately 50%. [ABSTRACT FROM AUTHOR]

Background: Because only limited evidence suggests that elastic stockings prevent the post-thrombotic syndrome in patients with symptomatic deep venous thrombosis (DVT), these stockings are not widely used. Objective: To evaluate the efficacy of compression elastic stockings for prevention of the post-thrombotic syndrome in patients with proximal DVT. Design: Randomized, controlled clinical trial. Setting: University hospital. Patients: 180 consecutive patients with a first episode of symptomatic proximal DVT who received conventional anticoagulant treatment. Interventions: Before discharge, patients were randomly assigned to wear or not wear below-knee compression elastic stockings (30 to 40 mm Hg at the ankle) for 2 years. Follow-up was performed for up to 5 years. Measurements: The presence and severity of the post-thrombotic syndrome were scored by using a standardized scale. Results: Post-thrombotic sequelae developed in 44 of 90 controls (severe in 10) and in 23 of 90 patients wearing elastic stockings (severe in 3). All but 1 event developed in the first 2 years. The cumulative incidence of the post-thrombotic syndrome in the control group versus the elastic stockings group was 40.0% (95% CI, 29.9% to 50.1%) versus 21.1% (CI, 12.7% to 29.5%) after 6 months, 46.7% (CI, 36.4% to 57.0%) versus 22.2% (CI, 13.8% to 30.7%) after 1 year, and 49.1% (CI, 38.7% to 59.4%) versus 24.5% (CI, 15.6% to 33.4%) after 2 years. After adjustment for baseline characteristics, the hazard ratio for the post-thrombotic syndrome in the elastic stockings group compared with controls was 0.49 (CI, 0.29 to 0.84; P = 0.011). Limitations: This study lacked a double-blind design. Conclusions: Post-thrombotic sequelae develop in almost half of patients with proximal DVT. Below-knee compression elastic stockings reduce this rate by approximately 50%. [ABSTRACT FROM AUTHOR]

Background: The optimum duration of anticoagulant therapy after an episode of deep venous thrombosis (DVT) is controversial. Contributing to the controversy is uncertainty about whether residual venous thrombosis, as assessed by repeated ultrasonography over time, increases the risk for recurrent thromboembolism. Objective: To determine the risk for recurrent thromboembolism in patients who have persistent residual thrombosis compared with patients who have early vein recanalization. Design: Prospective cohort study. Setting: A university hospital in Padua, Italy. Patients: 313 consecutive symptomatic outpatients with proximal DVT who received conventional short-term anticoagulation. Measurements: Ultrasonographic assessment of the common femoral and popliteal veins was performed 3 months after acute DVT in all patients and at 6, 12, 24, and 36 months in patients found to have residual venous thrombosis. Veins were considered recanalized if they were 2.0 mm or less in diameter on a single test or 3.0 mm or less in diameter on two consecutive tests. Recurrent thromboembolism was assessed during a 6-year period. Results: The cumulative incidence of normal results on ultrasonography was 38.8% at 6 months, 58.1% at 12 months, 69.3% at 24 months, and 73.8% at 36 months. Of 58 recurrent episodes, 41 occurred while the patient had residual thrombosis. The hazard ratio for recurrent thromboembolism was 2.4 (95% CI, 1.3 to 4.4; P = 0.004) for patients with persistent residual thrombosis versus those with early vein recanalization. Conclusions: Residual venous thrombosis is an important risk factor for recurrent thromboembolism. Ultrasonographic assessment of residual venous thrombosis may help clinicians modify the duration of anticoagulation in patients with DVT. [ABSTRACT FROM AUTHOR]

Background: The standard diagnostic approach in patients with suspected deep vein thrombosis is to repeat the compression ultrasonography after 1 week in all patients with an initial normal result. We hypothesized that a normal finding of a D-dimer assay safely obviates the need for repeated ultrasonography. In addition, we evaluated the potential value of a pretest probability assessment for this purpose. Methods: At presentation, consecutive outpatients with suspected thrombosis underwent independent assessment by means of ultrasonography of the proximal veins, a wholeblood D-dimer assay, and a pretest clinical model. Patients with normal ultrasonographic findings and an abnormal D-dimer assay result were scheduled for repeated ultrasonography. We evaluated the incidence of symptomatic venous thromboembolic complications during a 3-month follow-up, and the value of clinical pretest probability with ultrasonography or D-dimer assay in scenario analyses. Results: We studied 1756 patients with prevalence of thrombosis of 22%. At entry, results of the D-dimer assay and ultrasonographywere normal in 828 patients (47%). Of these, 6 returned with confirmed symptomatic venous thromboembolism (complication rate, 0.7%; 95% confidence interval [CI], 0.3%-1.6%). Repeated ultrasonography was avoided in 61% of the patients with an initial normal test result. Scenario analyses disclosed that the complication rate was 1.6% (95% CI, 0.8%-2.6%) in those with a low clinical pretest probability and a normal result of ultrasonography at referral, whereas this figure was 1.8% (95% CI, 0.9%-3.3%) in patients with a low clinical probability result and a normal result of the D-dimer assay at referral. Conclusions: It is safe to withhold repeated ultrasonography in patients with suspected deep vein thrombosis who have normal results of ultrasonograpy and the SimpliRED D-dimer assay at presentation. The combination of a low clinical pretest probability with a normal result of... [ABSTRACT FROM AUTHOR]

COVID-19 is an infection due to SARS-CoV-2; this virus has been identified as the cause of the present pandemic. Several typical characteristics are present in this infection, in particular pneumonia with possible lung failure, but atypical clinical presentations are being described daily by physicians around the world. Ground-glass opacities with pneumonia are the most common and dangerous presentations of the COVID-19 disease, and they are usually associated with positive nasopharyngeal swab (NPS) tests with detectable SARS-CoV-2 viral RNA. Compared to the general population, hospital workers have been at a greater risk of infection ever since the first patients were hospitalized. However, hospital workers have also been reported as having COVID-like symptoms despite repeated negative swab tests but having tested positive for SARS-CoV-2 antibodies with serological tests. We can postulate that a COVID-like syndrome is possible, in particular in hospital workers, that is characterized by symptoms similar to those of COVID-19, but with repeated negative nasopharyngeal swabs. These repeated negative NSPs make the difference in daily clinical management with people that experienced a single false negative nasopharyngeal swab; furthermore, a clear clinical differentiation of these situations is still lacking in the literature. For this reason, here, we report our main findings from a cohort of patients with a COVID-like syndrome compared to a similar group affected by typical COVID-19. [ABSTRACT FROM AUTHOR]