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Loneliness, Social Isolation, and Healthcare Utilization in the General Population
No full textObjectives Due to increasing pressure on healthcare resources, knowledge of factors that affect healthcare utilization (HCU) is important. However, the evidence of a longitudinal association between loneliness and social isolation respectively, and HCU is limited. The present prospective cohort study investigated the association of loneliness and social isolation with HCU in the general population over time. Methods Data from the 2013 Danish “How are you?" survey (n = 27.501) were combined with individual-level register data with almost complete follow-up over a 6-year follow-up period (2013-2018). Negative binomial regression analyses were performed while adjusting for baseline demographics and pre-existing chronic disease. Results Loneliness measured was significantly associated with more general practice contacts (incident-rate ratio (IRR) = 1.03, 95% confidence interval (CI) [1.02, 1.04]), more emergency treatments (IRR = 1.06, 95% CI [1.03, 1.10]), more emergency admissions (IRR = 1.06, 95% CI [1.03, 1.06]), and hospital admission days (IRR=1.05, 95% CI [1.00, 1.11]) across the 6-year follow-up period. No significant associations were found between social isolation and HCU with one minor exception, in which social isolation was associated with fewer planned outpatient treatments (IRR = .97, 95% CI [.94, .99]). Wald test demonstrated that the association of loneliness with emergency admissions and hospital admissions days was not significantly different from the effects of social isolation on those outcomes. Conclusions Our findings suggest that loneliness slightly increased the number of general practice contacts and emergency room treatments. Overall, the effects of loneliness and social isolation on HCU were small
Looking into the IL-1 of the storm: Are inflammasomes the link between immunothrombosis and hyperinflammation in cytokine storm syndromes?
No full textInflammasomes and the interleukin (IL)-1 family of cytokines are key mediators of both inflammation and immunothrombosis. Inflammasomes are responsible for the release of the pro-inflammatory cytokines IL-1β and IL-18, as well as releasing tissue factor (TF), a pivotal initiator of the extrinsic coagulation cascade. Uncontrolled production of inflammatory cytokines results in what is known as a “cytokine storm” leading to hyperinflammatory disease. Cytokine storms can complicate a variety of diseases and results in hypercytokinemia, coagulopathies, tissue damage, multi-organ failure and death. Patients presenting with cytokine storm syndromes have a high mortality rate, driven in part by disseminated intravascular coagulation (DIC). Whilst our knowledge on the factors propagating cytokine storms is increasing, how cytokine storm influences DIC remains unknown, and therefore treatments for diseases, where these aspects are a key feature are limited, with most targeting specific cytokines. Currently, no therapies target the immunothrombosis aspect of hyperinflammatory syndromes. Here we discuss how targeting the inflammasome and pyroptosis may be a novel therapeutic strategy for the treatment of hyperinflammation and its associated pathologies
Concurrent multi-scale modeling of granular materials: Role of coarse-graining in FEM-DEM coupling
No full textThe finite element method (FEM) is commonly used for modeling continuum media, while particle simulation methods like the so-called discrete element method (DEM) are used for discrete systems. Coupling the discrete (DEM) and continuum (FEM) methods is conventionally achieved through a direct mapping between discrete particles and finite elements. Coarse-graining (CG) is a micro-macro transition method (discrete to continuum) that maps discrete particle data onto smooth, differentiable fields that satisfy the continuum equations. By choosing an appropriate length scale (the coarse-graining width c), the coarse-grained fields are then homogenized and projected onto a FEM spatial discretization.This concept is utilized here to reformulate FEM-DEM coupling methods, both surface and volume, where in the limiting case of c → 0, the classical coupling is recovered. For surface coupling, the discrete particle-surface contact forces are first mapped onto a continuous surface traction field (using CG) which is then coupled to the continuum FEM model. For volume coupling (also known as the Arlequin framework), the homogenization operators are enriched with CG functions, offering a non-local coupling approach between discrete particles, their continuum fields, and the finite element formulation.The CG enrichment represents a new strategy that consists of (1) a particle-to-continuum mapping and (2) a continuum-to-continuum coupling based on “CG-enriched homogenization” (CGH). It is shown for surface coupling that the CG-enriched formulation not only leads to more accurate results, conserving symmetry, but also reduces energies generated by the coupling. For volume coupling, there is consistently less numerical dissipation with than without CG-enrichment, especially when the load contains high-frequency content. Finally, the optimal CG widths are identified for very simple test cases, with which the surface/volume coupling performs best.CGH can be potentially extended beyond the present examples, by considering other continuum fields (e.g., higher-order) and equations (e.g., multi-physics), and used to formulate other concurrent multi-scale modeling methods
Prognostic and predictive factors for locoregional and systemic therapies in hepatocellular carcinoma
No full textHepatocellular carcinoma (HCC) is a growing health concern, with an estimated global incidence of over 1 million by 2025. In its intermediate and advanced stages, HCC remains a challenging condition to treat, despite a recently expanded array of systemic therapies, which continues to grow. Extensive efforts have accordingly been made to identify predictive factors to guide treatment decisions. However, currently only one predictive biomarker is in widespread clinical use, namely elevated alpha-fetoprotein for second-line systemic therapy with ramucirumab. This article reviews known prognostic and predictive biomarkers for patients with HCC who are treated with locoregional and systemic therapies, including recent controversies around the potential impact of HCC aetiology on the efficacy of systemic therapies
Recall of exposure in UK farmers and pesticide applicators:trends with follow-up time
No full textBACKGROUND: Occupational epidemiological studies on pesticide use commonly rely on self-reported questionnaire or interview data to assess exposure. Insight into recall accuracy is important, as misclassification of exposures due to imperfect recall can bias risk estimates.METHODS: We assessed the ability of workers in three UK cohorts (Prospective Investigation of Pesticide Applicators' Health [PIPAH], Pesticide Users' Health Study [PUHS], and Study of Health in Agricultural Work [SHAW]) to remember their working history related to pesticide exposure over time periods ranging from 3 to 14 years prior. During 2019-2020, cohort participants were re-surveyed using a similar questionnaire to that used previously. We compared recall of responses at follow-up to those reported at baseline related to crops/areas of work, use of personal protective equipment (PPE) items, hygiene habits, frequency of pesticide use, and application method. To assess the extent of recall, we used sensitivity, specificity, the percentage of overall agreement, and area under the curve (AUC) values. We also examined the presence of over or underestimation of recalled years, and days and hours per year, of working with pesticides using geometric mean ratios (GMR) and regression analysis to investigate any trends based on demographic characteristics.RESULTS: There were 643 individuals who completed both the baseline and follow-up surveys in the three cohorts with response rates ranging from 17 to 46%. There was a strong correlation (rho = 0.77) between the baseline and recalled years working with pesticides, though higher values were reported at follow-up (GMR = 1.18 [95% confidence interval: 1.07-1.30]) with no consistent differences by demographic characteristics. There was stronger agreement in the recalled days compared to hours per year in two of the cohorts. Recall for a number of exposure determinants across short and longer periods entailed overall agreement of >70%, though with some differences: for example, sensitivity for long-term recall of crops was poor (<43% in PUHS), whereas short-term recall of hygiene practices was good (AUC range = 0.65-1.00 in PIPAH).CONCLUSION: Results indicate that recall ability may deteriorate over a longer period. Although low-response rates may require these findings to be interpreted with caution, recall for a number of exposure determinants appeared reliable, such as crops and hygiene practices within 3 years, as well as days per year working with pesticides.</p
Modelling annual scintillation arc variations in PSR J1643−1224 using the large european array for pulsars
No full textIn this work we study variations in the parabolic scintillation arcs of the binary millisecond pulsar PSR J1643−1224 over five years using the Large European Array for Pulsars (LEAP). The 2D power spectrum of scintillation, called the secondary spectrum, often shows a parabolic distribution of power, where the arc curvature encodes the relative velocities and distances of the pulsar, ionised interstellar medium (IISM), and Earth. We observe a clear parabolic scintillation arc which varies in curvaturethroughout the year. The distribution of power in the secondary spectra are inconsistent with a single scattering screen which is fully 1D, or entirely isotropic. We fit the observed arc curvature variations with two models; an isotropic scattering screen, and a model with two independent 1D screens. We measure the distance to the scattering screen to be in the range 114-223 pc, depending on the model, consistent with the known distance of the foreground large-diameter HII region Sh 2-27 (112 ± 17 pc), suggesting that it is the dominant source of scattering. We obtain only weak constraints on the pulsar’s orbital inclination and angle of periastron, since the scintillation pattern is not very sensitive to the pulsar’s motion, since the screen is much closer to the Earth than the pulsar. More measurements of this kind - where scattering screens can be associated with foreground objects - will help to inform the origins and distribution of scattering screens within our galaxy.Key words: pulsars: general – pulsars:individual ( PSR J1643−1224) – ISM:HII regio
ESBMC-Solidity: An SMT-Based Model Checker for Solidity Smart Contracts
No full textSmart contracts written in Solidity are programs used in blockchain networks, such as Etherium, for performing transactions. However, as with any piece of software, they are prone to errors and may present vulnerabilities, which malicious attackers could then use. This paper proposes a solidity frontend for the efficient SMT-based context-bounded model checker (ESBMC), named ESBMC-Solidity, which provides a way of verifying such contracts with its framework. A benchmark suite with vulnerable smart contracts was also developed for evaluation and comparison with other verification tools. The experiments performed here showed that ESBMC-Solidity detected all vulnerabilities, was the fastest tool, and provided a counterexample for each benchmark. A demonstration is available at https://youtu.be/3UH8_1QAVN0
Wit4Java: A Violation-Witness Validator for Java Verifiers
No full textWe describe and evaluate a violation-witness validator for Java verifiers called Wit4Java. It takes a Java program with a safety property and the respective violation-witness output by a Java verifier to generate a new Java program whose execution deterministically violates the property. We extract the value of the program variables from the counterexample represented by the violation witness and feed this information back into the original program. In addition, we have two implementations for instantiating source programs by injecting counterexamples. Experimental results show that Wit4Java can correctly validate the violation-witnesses produced by JBMC and GDart in a few seconds
Quantifying the Impacts of Modelling Assumptions on Accuracy and Computational Efficiency for Integrated Water-Energy System Simulations Under Uncertain Climate
No full textJointly managing water and energy systems, rather than treating each system independently, is recognised as an approach that can lead to a more cost-effective and reliable supply, which is particularly critical in water-rich and developing countries. This has motivated the development of various integrated water-energy simulators, each one catering for specific modelling needs through the use of specific sets of modelling assumptions, e.g., representing water and energy with balance equations, or dedicated river flow and power network equations. In this context, it becomes critical to assess the effectiveness of different modelling assumptions to improve the design of water-energy simulators. In particular, it is important to develop a methodology that can identify, based on a systematic assessment process, the portfolios of modelling assumptions that better capture the uncertain future conditions in the water and energy sectors, e.g., climate-driven stresses and shocks such as water scarcity, temperature rise, etc. To address this challenge, this paper proposes a Mixed Integer Linear Programming (MILP) integrated water-energy system simulation methodology designed to adapt and quantify different modelling assumptions under various weather-related conditions (e.g., water scarcity and high temperatures). The models were developed to capture the characteristics of non-pressurised water systems (e.g., channels and rivers) and electricity systems. The methodology is used to investigate typical modelling assumptions (e.g., temporal resolutions and water and power system models) and novel approaches to model the impacts of high temperatures on generation capacity to capture the effects of extreme weather on power generation. The methodology is demonstrated on the Ghanaian integrated water-energy system. The results highlight the benefits in terms of computational costs and modelling accuracy, of the customisable simulation, and provide guidance to select adequate modelling assumptions
Ventricular arrhythmias and sudden death in non-ischemic dilated cardiomyopathy: matter of sex or scar?
No full textAimsTo evaluate the association between sex and ventricular arrhythmias (VA) or sudden death (SD) in non-ischemic dilated cardiomyopathy, including analysis of potential confounders.MethodsRetrospective cohort study of consecutive patients with DCM referred for cardiac magnetic resonance (CMR) at two tertiary hospitals. The primary combined endpoint encompassed sustained VA, appropriate ICD therapies, resuscitated cardiac arrest and SD. ResultsWe included 1165 patients with median follow-up of 36 months (interquartile range 20-58 months). The majority of patients (66%) were males. Males and females had similar LVEF but the prevalence of late gadolinium enhancement (LGE) at CMR was significantly higher among males (48% vs 30%, p<0.001). Males had higher cumulative incidence of the primary endpoint (8% vs 4%, p=0.02) and male sex was a significant predictor of the primary endpoint at univariate analysis (HR 1.93, p=0.02). However, LGE had a major confounding effect in the association between sex and the primary outcome: the HR of male sex adjusted for LGE was 1.29 (p=0.37). LGE+ females had significantly higher cumulative incidence of the primary endpoint than LGE- males (13% vs 1.8%, p<0.001).ConclusionsIn patients with DCM, the prevalence of LGE is significantly higher among males, implying a major confounding effect in the association between male sex and VA or SD. LGE+ females have significantly higher risk than LGE- males. These data do not support the inclusion of sex into risk-stratification algorithms for VA or SD in DCM.<br/