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Depression and anxiety in a real-world psoriatic arthritis longitudinal study. Should we focus more on patients’ perception?
No full textObjectives: Longitudinal studies using validated tools to evaluate depression and anxiety in psoriatic arthritis (PsA) are lacking. We aimed to estimate their course in PsA and to examine possible associations with disease-related parameters and patient-reported outcomes (PROs).Methods: PsA patients attending two outpatient rheumatology clinics were consecutively enrolled (January 2019-June 2021, n=128). The hospital anxiety and depression scale (HADS) was used at two sequential visits (mean±SD: 10±6 months) to prospectively assess depression (HADS-Depression) and anxiety (HADS-Anxiety) (cut-off scores≥11). Associations with demographic, clinical, laboratory features and PROs for quality of life (QoL) (EQ-5D), functional status (HAQ-DI) and nocebo-behaviour (Q-No) were examined. ‘Change’ was the difference between values at the first and second visit.Results: Prevalence of depression and anxiety at the first visit was 19.5% and 21.1%, respectively. Depression was associated with EQ-5D [OR (95% CI): 1.70 (1.02-2.59), p=0.019] and anxiety with EQ-5D [1.81 (1.20 to 2.72), p=0.005], nocebo-behaviour [1.19 (1.01-1.40), p=0.04] and current corticosteroid use [6.95 (1.75-27.59), p=0.006]. At the second visit, HADS-Depression and HADS-Anxiety scores were improved in 40.9% and 41.9% of patients, respectively. While no associations were found for HADS-Anxiety score change, changes in HADS-Depression score correlated with changes in subjective (tender joint count, r= 0.204, p=0.049; PtG, r= 0.236, p=0.023; patient pain assessment, r= 0.266, p=0.01) but not objective (swollen joint count, ESR, CRP) parameters of disease activity.Conclusion: In PsA, depression and anxiety are associated with worse PROs, including QoL. Subjective parameters of disease activity parallel course of depression.<br/
Second coordination sphere effects on the mechanistic pathways for dioxygen activation by a ferritin: involvement of a Tyr radical and the identification of a cation binding site
No full textFerritins are ubiquitous diiron enzymes involved in iron(II) detoxification and oxidative stress responses and can act as metabolic iron stores. The overall reaction mechanisms of ferritin enzymes are still unclear, particularly concerning the role of the conserved, near catalytic center Tyr residue. Thus, we carried out a computational study of a ferritin using a large cluster model of well over 300 atoms including its first- and second-coordination sphere. The calculations reveal important insight into the structure and reactivity of ferritins. Specifically, the active site Tyr residue delivers a proton and electron in the catalytic cycle prior to iron(II) oxidation. In addition, the calculations highlight a likely cation binding site at Asp65, which through long-range electrostatic interactions, influences the electronic configuration and charge distributions of the metal center. The results are consistent with experimental observations but reveal novel detail of early mechanistic steps that lead to an unusual mixedvalent iron(III)-iron(II) center
Follow-up regimes for sick-listed employees: a comparison of nine north-western European countries
No full textThe Covid-19 pandemic has revealed the importance of social protection systems, including income security, when health problems arise. The aims of this study are to compare the follow-up regimes for sick-listed employees across nine European countries, and to conduct a qualitative assessment of the differences with respect to burden and responsibility sharing between the social protection system, employers and employees. The tendency highlighted is that countries with shorter employer periods of sick-pay typically have stricter follow-up responsibility for employers because, in practice, they become gatekeepers of the public sickness benefit scheme. In Germany and the UK, employers have few requirements for follow-up compared with the Nordic countries because they bear most of the costs of sickness absence themselves. The same applies in Iceland, where employers carry most of the costs and have no obligation to follow up sick-listed employees. The situation in the Netherlands is paradoxical: employers have strict obligations in the follow-up regime even though they cover all the costs of the sick-leave themselves. During the pandemic, the majority of countries have adjusted their sick-pay system and increased coverage to reduce the risk of spreading Covid-19 because employees are going to work sick or when they should self-quarantine, except for the Netherlands and Belgium, which considered that the current schemes were already sufficient to reduce that risk
Dynamics of electrostatic interaction and electrodiffusion in a charged thin film with nanoscale physicochemical heterogeneity: implications for low-salinity waterflooding
No full textThe slow kinetics of wettability alteration toward a more water-wetting state by low-salinity waterflooding (LSWF) in oil-brine-rock (OBR) systems is conjectured to be pertinent to the electrokinetic phenomena in the thin brine film. We hypothesize that the nanoscale physicochemical heterogeneities such as surface roughness and surface charge heterogeneity at the rock/brine interface control further the dynamics of electrodiffusion and electrostatic disjoining pressure (Πel), thus the time-scale and the magnitude of the low salinity effect (LSE). Film-scale computational fluid dynamics (CFD) simulations were performed to demonstrate this. The coupled Poisson-Nernst-Planck (PNP) equations were solved numerically in a thin water film confined between a solid surface and oil, both negatively charged. The solid surface is representative of quartz/kaolinite with patchwise physicochemical heterogeneity. The electrical properties of the oil are representative of a crude-oil sample. The OBR system is initially under chemical equilibrium with high salinity (HS) brine, then is exposed to low salinity (LS) brine. The time-scale of reaching chemical equilibrium under LS, and the evolution of electric potential were investigated. We find that surface roughness increases the diffusion time up to 3-fold due to increased tortuosity. Also, the effect of surface roughness and surface charge heterogeneity on the effective diffusioncoefficient (Deff) is minor. While surface roughness and surface charge 1 heterogeneity affect the disjoining pressure (Πel) significantly, the influence of surface roughness on Πel is more pronounced under HS than LS conditions. In contrast, the effect of surface charge heterogeneity (introduced by kaolinite patches on quartz) is more appreciable under LS than HS. Our findings imply that the LS effect can be enhanced in rough, heterogeneously charged systems like clayey sandstone, although its magnitude depends on the charge density of the roughness. We introduce two scaling factors, namely the effective diffusion coefficient (Deff) and the retardation coefficient (ω), to upscale the nanoscale results to pore-scale and beyond
Rifting and recharge as triggers of the mixed basalt-1 rhyolite Halarauður ignimbrite eruption (Krafla, Iceland)
No full textWe present a petrologic study of the ca. 110 ka Halarauður eruption (7 ± 6 km3 magma), associated with collapse of Krafla caldera in northeast Iceland. Whole-rock compositions of juvenile Halarauður products span a continuous range between quartz tholeiite basalt (50.0 wt% SiO2, 5.0 wt% MgO; Mg# 42) and rhyolite (74.6 wt% SiO2). Linear correlations between all major elements are consistent with two-component mixing of subequal volumes of these endmember magmas, whereas correlations between trace elements are influenced by diffusive fractionation during chaotic mixing. Evolved compositions (andesite to rhyolite) and compositional heterogeneity are typical of early-erupted units, reflecting tapping of the upper, more silicic regions of a compositionally heterogeneous reservoir undergoing chaotic mixing. Later-erupted deposits are more compositionally homogeneous and grade smoothly upward from andesite to basalt, reflecting tapping of denser hybrid magma and uncontaminated basalt from lower in the chamber. All erupted products host <1-2 modal% macrocrysts, implying storage at near-liquidus temperatures. Geobarometry and MELTS modeling suggest shallow storage pressures of ~200 MPa (~8 km depth) for the quartz tholeiite. Plagioclase (An60-76) and augite (Mg# 68-75) macrocrysts crystallized from this basalt during shallow storage, while sparse glomerocrysts (plagioclase ± augite ± olivine ± orthopyroxene) in late-erupted basaltic material are derived from disaggregated cumulate mush and include more primitive compositions. Occasional narrow sodic rims on plagioclase crystals from the quartz tholeiite record short periods of re-equilibration with hybrid magmas during mixing, constrained by experimental growth rates as at most two months and possibly as short as tens of hours. A second population of calcic plagioclase (cores An83-91) with adhering primitive basaltic glass selvages (Mg# 53-59) occurs sparsely in deposits of the first eruptive phase and is scarce or absent in later-erupted units, providing evidence for eruption of a second, more primitive basalt that was of insufficient volume to skew whole-rock mixing trends. Nucleation delay models suggest that the absence of overgrowth rims or quench crystals in these glassy basaltic selvages reflect residence times of a few hours at rhyolitic temperatures before eruption. Short basalt-rhyolite mixing timescales reflect rapid destabilization of the magmatic system and triggering of the eruption by mafic recharge. The ascent of both primitive and evolved basaltic magmas from depth mirrors events in recent volcano-tectonic episodes in the north of Iceland, suggesting that mafic recharge was driven by a plate boundary rifting event
Emotionally Based School Non-Attendance: Two Successful Returns to School Following Lockdown
No full textEmotionally based school non-attendance (EBSNA) needs are complex, with a distinctive combination of risk factors affecting each individual. This study presents an exploration of the perceived facilitators to successful returns to school for two primary-aged children who had previously experienced anxiety around school attendance. The perspectives of parents, school staff, and educational psychologists were gathered using semi-structured interviews to identify effective support. A reflexive thematic analysis was conducted to generate themes. Findings demonstrate that the support in each case was highly individualised. Key facilitators considered to achieve this included: effective home-school communication; taking a functional approach; engaging other professional support; cultivating positive relationships; and practitioners regularly reflecting on their practice. The significant overlap between themes supports an interactionist, ecological model of early identification and intervention for EBSNA difficulties. Implications for practitioners include the need to ensure a reflective, individualised approach, and the importance of facilitating the home-school relationship.Keywords: emotionally based school non-attendance; anxiety; school absenteeism; educational psychology; intervention<br/
Developing an understanding of sophorolipid synthesis through application of a central composite design model
No full textA key barrier to market penetration for sophorolipid biosurfactants is the ability to improve productivity and utilise alternative feedstocks to reduce the cost of production. To do this, a suitable screening tool is required that is able to model the interactions between media components and alter conditions to maximise productivity. In the following work a central composite design is applied to analyse the effects of altering glucose, rapeseed oil, cornsteep liquor and ammonium sulfate concentrations on sophorolipid production with Starmerella bombicola ATCC 222144 after 168 h. Sophorolipid production was analysed using standard least squares regression and the findings related to the growth (OD600) and broth conditions (glucose, glycerol and oil concentration). An optimum media composition was found that was capable of producing 39.5 g/L sophorolipid. Nitrogen and rapeseed oil sources were found to be significant, linked to their role in growth and substrate supply respectively. Glucose did not demonstrate a significant effect on production despite its importance to biosynthesis and its depletion in the broth within 96 h, instead being replaced by glycerol (via triglyceride breakdown) as the hydrophilic carbon source at the point of glucose depletion. A large dataset was obtained and a regression model with applications towards substrate screening and process optimisation developed
Did the Siebel Systems Case Limit the SEC's Ability to Enforce Regulation Fair Disclosure?
No full textWe examine whether a shock to the enforceability of Regulation Fair Disclosure (Reg FD) limited its ability to restrict the flow of private information between managers and investors. While prior work provides evidence that Reg FD reduced managers’ selective disclosure of material information immediately following its promulgation, we posit that private information flows returned as a result of the SEC’s public enforcement failure in SEC v. Siebel Systems, Inc. Using multiple settings, we find consistent evidence suggesting that Siebel changed the cost-benefit tradeoff for Reg FD compliance and effectively reversed the initial effects of the regulation. We also find that Siebel disrupted the equilibrium of selective disclosure activity, resulting in an unleveling effect among investors with respect to private information advantages. Finally, we find that Siebel also had real effects by altering managers’ capital structure decisions. Our findings run counter to the prevailing “mosaic theory” and gradual learning explanations for private information advantages in the extended post-Reg FD period and highlight the importance of enforcement in achieving intended regulatory outcomes
A Novel Borinate Ester Copolymer for Poly(Frustrated Lewis Pair) Gels
No full textThe versatile chemistry of boronic acid and boronate ester containing polymers has led to key applications in drug delivery, chemical sensing, and dynamic materials. However, their use in polymeric Frustrated Lewis pair (FLP) remains unreported. In this paper we report the synthesis of a novel fluorinated borinate ester copolymer which, when combined with a suitable Lewis basic copolymer, generates polymeric FLP network capable of responsive gelation. The borinate ester moiety, bis(pentafluorophenyl)borinic acid tetrafluorophenyl ester, was affixed to a polystyrene copolymer by a two-step post-polymerisation modification, which can be easily upscaled and purified. The Gutmann-Beckett method suggests these fluorinated borinate ester moieties are amongst the most Lewis acidic boron-containing polymers reported to date. Upon mixing with a Lewis basic copolymer poly(styrene-co-p-diphenylphosphino styrene), gelation cannot be achieved due to steric hindrance around the Lewis centres. However, network formation can be triggered by addition of small molecules such as diethylazodicarboxylate (DEAD) and cyclic ethers. The physical parameters and nature of the crosslinks of the gels prepared from different crosslinkers were probed by rheology. All networks demonstrated strong elastic behaviour, corresponding to covalently crosslinked materials. DEAD crosslinked gels displayed different behaviour to those triggered by cyclic ethers, indicating that mechanism of small molecule activation also plays an important role in the mechanical properties of poly(FLP) gels
FuSeBMC v4: Smart Seed Generation for Hybrid Fuzzing
No full textFuSeBMC is a test generator for finding security vulnerabilities in C programs. In Test-Comp 2021, we described a previous version that incrementally injected labels to guide Bounded Model Checking (BMC) and Evolutionary Fuzzing engines to produce test cases for code coverage and bug finding. This paper introduces an improved version of FuSeBMC that utilizes both engines to produce smart seeds. First, the engines run with a short time limit on a lightly instrumented version of the program to produce the seeds. The BMC engine is particularly useful in producing seeds that can pass through complex mathematical guards. Then, FuSeBMC runs its engines with extended time limits using the smart seeds created in the previous round. FuSeBMC manages this process in two main ways. Firstly, it uses shared memory to record the labels covered by each test case. Secondly, it evaluates test cases, and those of high impact are turned into seeds for subsequent test fuzzing. In this year’s competition, we participate in the Cover-Error, Cover-Branches, and Overall categories. The Test-Comp 2022 results show that we significantly increased our code coverage score from last year, outperforming all tools in all categories.<br/