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OBJECTIVES: This study investigated the relationship between numeracy skills and choice consistency in discrete choice experiments (DCEs). METHODS: A DCE was conducted to explore patients' preferences for kidney transplantation in Italy. Patients completed the DCE and answered three-item numeracy questions. A Heteroskedastic Multinomial Logit (HMNL) model was used to investigate the effect of numeracy on choice consistency. RESULTS: Higher numeracy skills were associated with greater choice consistency, increasing the scale to 1.63 (p<0.001), 1.39 (p<0.001), and 1.18 (p<0.001) for patients answering 3/3, 2/3, and 1/3 questions correctly, respectively, compared to those with no correct answers. This corresponded to 63%, 39%, and 18% more consistent choices, respectively. Accounting for choice consistency resulted in varying willingness-to-wait (WTW) estimates for kidney transplant attributes. Patients with the lowest numeracy (0/3) were willing to wait approximately 42 months [95% CI: 29.37, 54.68] for standard infectious risk, compared to 33 months [95% CI: 28.48, 38.09] for 1/3, 28 months [95% CI: 25.13, 30.32] for 2/3, and 24 months [95% CI: 20.51, 27.25] for 3/3 correct answers. However, WTW differences for an additional year of graft survival and neoplastic risk were not statistically significant across numeracy levels. Supplementary analyses of two additional DCEs on COVID-19 vaccinations and rheumatoid arthritis, conducted online, supported these findings: higher numeracy skills were associated with more consistent choices across different disease contexts and survey formats. CONCLUSIONS: The findings suggested that combining patients with varying numeracy skills could bias WTW estimates, highlighting the need to consider numeracy in DCE data analysis and interpretation.
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We developed a sensing strategy that mimics the bead-based electrogenerated chemiluminescence immunoassay. However, instead of the most common metal complexes, such as Ru or Ir, the luminophore is luminol. The electrogenerated chemiluminescence of luminol was promoted by in situ electrochemical generation of hydrogen peroxide at a boron-doped diamond electrode. The electrochemical production of hydrogen peroxide was achieved in a carbonate solution by an oxidation reaction, while at the same time, microbeads labelled with luminol were deposited on the electrode surface. For the first time, we proved that was possible to obtain light emission from luminol without its direct oxidation at the electrode. This new emission mechanism is obtained at higher potentials than the usual luminol electrogenerated chemiluminescence at 0.3-0.5 V, in conjunction with hydrogen peroxide production on boron-doped diamond at around 2-2.5 V (vs Ag/AgCl).
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BACKGROUND: Despite the potential for improved population mental health and wellbeing, the integration of mental health digital interventions has been difficult to achieve. In this qualitative systematic review, we aimed to identify barriers and facilitators to the implementation of digital technologies in mental healthcare systems, and map these to an implementation framework to inform policy development. METHODS: We searched Medline, Embase, Scopus, PsycInfo, Web of Science, and Google Scholar for primary research articles published between January 2010 and 2022. Studies were considered eligible if they reported barriers and/or facilitators to the integration of any digital mental healthcare technologies. Data were extracted using EPPI-Reviewer Web and analysed thematically via inductive and deductive cycles. RESULTS: Of 12,525 references identified initially, 81 studies were included in the final analysis. Barriers and facilitators were grouped within an implementation (evidence-practice gap) framework across six domains, organised by four levels of mental healthcare systems. Broadly, implementation was hindered by the perception of digital technologies as impersonal tools that add additional burden of care onto both providers and patients, and change relational power asymmetries; an absence of resources; and regulatory complexities that impede access to universal coverage. Facilitators included person-cantered approaches that consider patients' intersectional features e.g., gender, class, disability, illness severity; evidence-based training for providers; collaboration among colleagues; appropriate investment in human and financial resources; and policy reforms that tackle universal access to digital health. CONCLUSION: It is important to consider the complex and interrelated nature of barriers across different domains and levels of the mental health system. To facilitate the equitable, sustainable, and long-term digital transition of mental health systems, policymakers should consider a systemic approach to collaboration between public and private sectors to inform evidence-based planning and strengthen mental health systems. PROTOCOL REGISTRATION: The protocol is registered on PROSPERO, CRD42021276838.
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Tecnología Digital , Política de Salud , Servicios de Salud Mental , Investigación Cualitativa , Humanos , Servicios de Salud Mental/organización & administraciónRESUMEN
Electrogenerated chemiluminescence (ECL) stands out as a remarkable phenomenon of light emission at electrodes initiated by electrogenerated species in solution. Characterized by its exceptional sensitivity and minimal background optical signals, ECL finds applications across diverse domains, including biosensing, imaging, and various analytical applications. This review aims to serve as a comprehensive guide to the utilization of ECL in analytical applications. Beginning with a brief exposition on the theory at the basis of ECL generation, we elucidate the diverse systems employed to initiate ECL. Furthermore, we delineate the principal systems utilized for ECL generation in analytical contexts, elucidating both advantages and challenges inherent to their use. Additionally, we provide an overview of different electrode materials and novel ECL-based protocols tailored for analytical purposes, with a specific emphasis on biosensing applications.
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A sulfonated tris(1-phenylpyrazolato)iridium(III) complex ([Ir(sppz)3]3-) serves as a proof-of-concept non-emissive enhancer of the widely used ECL detection system of tris(2,2'-bipyridine)ruthenium(II) ([Ru(bpy)3]2+) with tri-n-propylamine (TPrA) co-reactant, acting through electrocatalysis of TPrA oxidation and efficient chemi-excitation of the luminophore. Using self-interference ECL spectroscopy, we show that the enhancer extends diffusion of the required electrogenerated precursors from the electrode surface. Previously reported enhancement through these pathways has been confounded by the inherent ECL of the enhancer, but the increase in [Ru(bpy)3]2+ ECL intensity using [Ir(sppz)3]3- was obtained without its concomitant emission. The most prominent enhancement (11-fold) occurred at low potentials associated with the 'indirect' co-reactant ECL pathway, which translated to between 2- and 6-fold enhancement when the luminophore was immobilised on microbeads as a general model for enhanced ECL assays.
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As an electrochemical technique offering an optical readout, electrochemiluminescence (ECL) evolved recently into a powerful microscopy technique with the visualization of a wide range of microscopic entities. However, the dynamic imaging of transient ECL events did not receive intensive attention due to the limited number of electrogenerated photons. Here, the reaction kinetics of the model ECL bioassay system was revealed by dynamic imaging of single [Ru(bpy)3]2+-functionalized beads in the presence of the efficient tripropylamine coreactant. The time profile behavior of ECL emission, the variations of the ECL layer thickness, and the position of maximum ECL intensity over time were investigated, which were not achieved by static imaging in previous studies. Moreover, the dynamics of the ECL emission were confronted with the simulation. The reported dynamic ECL imaging allows the investigation of the ECL kinetics and mechanisms operating in bioassays and cell microscopy.
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Luminiscencia , Fotometría , Mediciones Luminiscentes , Microscopía , Técnicas Electroquímicas/métodosRESUMEN
Electrochemiluminescence (ECL) microscopy is an emerging technique with new applications such as imaging of single entities and cells. Herein, we have developed a bimodal and bicolor approach to record both positive ECL (PECL: light-emitting object on dark background) and shadow label-free ECL (SECL: nonemissive object shadowing the background luminescence) images of single cells. This bimodal approach is the result of the simultaneous emissions of [Ru(bpy)3]2+ used to label the cellular membrane (PECL) and [Ir(sppy)3]3- dissolved in solution (SECL). By spectrally resolving the ECL emission wavelengths, we recorded the images of the same cells in both PECL and SECL modes using the [Ru(bpy)3]2+ (λmax = 620 nm) and [Ir(sppy)3]3- (λmax = 515 nm) luminescence, respectively. PECL shows the distribution of the [Ru(bpy)3]2+ labels attached to the cellular membrane, whereas SECL reflects the local diffusional hindrance of the ECL reagents by each cell. The high sensitivity and surface-confined features of the reported approach are demonstrated by imaging cell-cell contacts during the mitosis process. Furthermore, the comparison of PECL and SECL images demonstrates the differential diffusion of tri-n-propylamine and [Ir(sppy)3]3- through the permeabilized cell membranes. Consequently, this dual approach enables the imaging of the morphology of the cell adhering on the surface and can significantly contribute to multimodal ECL imaging and bioassays with different luminescent systems.
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Mediciones Luminiscentes , Microscopía , Mediciones Luminiscentes/métodos , Fotometría , Luminiscencia , Membrana CelularRESUMEN
PURPOSE: Skeletal dysplasias are rare genetic disorders that are characterized by abnormal development of bone and cartilage. There are multiple medical and non-medical treatments for specific symptoms of skeletal dysplasias e.g. pain, as well as corrective surgical procedures to improve physical functioning. The aim of this paper was to develop an evidence-gap map of treatment options for skeletal dysplasias, and their impact on patient outcomes. METHODS: We conducted an evidence-gap map to identify the available evidence on the impact of treatment options on people with skeletal dysplasias on clinical outcomes (such as increase in height), and dimensions of health-related quality of life. A structured search strategy was applied to five databases. Two reviewers independently assessed articles for inclusion in two stages: titles and abstracts (stage 1), and full text of studies retained at stage 2. RESULTS: 58 studies fulfilled our inclusion criteria. The included studies covered 12 types of skeletal dysplasia that are non-lethal with severe limb deformities that could result in significant pain and numerous orthopaedic interventions. Most studies reported on the effect of surgical interventions (n = 40, 69%), followed by the effect of treatments on dimensions of health quality-of-life (n = 4, 6.8%) and psychosocial functioning (n = 8, 13.8%). CONCLUSION: Most studies reported on clinical outcomes from surgery for people living with Achondroplasia. Consequently, there are gaps in the literature on the full range of treatment options (including no active treatment), outcomes and the lived experience of people living with other skeletal dysplasias. More research is warranted to examine the impact of treatments on health-related quality-of-life of people living with skeletal dysplasias, including their relatives to enable them to make preference- and valued based decisions about treatment.
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Lagunas en las Evidencias , Calidad de Vida , Humanos , Calidad de Vida/psicología , DolorRESUMEN
BACKGROUND: The initial policy response to the COVID-19 pandemic has differed widely across countries. Such variability in government interventions has made it difficult for policymakers and health research systems to compare what has happened and the effectiveness of interventions across nations. Timely information and analysis are crucial to addressing the lag between the pandemic and government responses to implement targeted interventions to alleviate the impact of the pandemic. METHODS: To examine the effect government interventions and technological responses have on epidemiological and economic outcomes, this policy paper proposes a conceptual framework that provides a qualitative taxonomy of government policy directives implemented in the immediate aftermath of a pandemic announcement and before vaccines are implementable. This framework assigns a gradient indicating the intensity and extent of the policy measures and applies the gradient to four countries that share similar institutional features but different COVID-19 experiences: Italy, New Zealand, the United Kingdom and the United States of America. RESULTS: Using the categorisation framework allows qualitative information to be presented, and more specifically the gradient can show the dynamic impact of policy interventions on specific outcomes. We have observed that the policy categorisation described here can be used by decision-makers to examine the impacts of major viral outbreaks such as SARS-CoV-2 on health and economic outcomes over time. The framework allows for a visualisation of the frequency and comparison of dominant policies and provides a conceptual tool to assess how dominant interventions (and innovations) affect different sets of health and non-health related outcomes during the response phase to the pandemic. CONCLUSIONS: Policymakers and health researchers should converge toward an optimal set of policy interventions to minimize the costs of the pandemic (i.e., health and economic), and facilitate coordination across governance levels before effective vaccines are produced. The proposed framework provides a useful tool to direct health research system resources and build a policy benchmark for future viral outbreaks where vaccines are not readily available.
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COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Pandemias/prevención & control , Políticas , Brotes de EnfermedadesRESUMEN
Three recently synthesized neutral dinuclear carbonyl manganese complexes with the pyridazine bridging ligand, of general formula [Mn2(µ-ER)2(CO)6(µ-pydz)] (pydz = pyridazine; E = O or S; R = methyl or phenyl), have been investigated by cyclic voltammetry in dimethylformamide and acetonitrile both under an inert argon atmosphere and in the presence of carbon dioxide. This family of Mn(I) compounds behaves interestingly at negative potentials in the presence of CO2. Based on this behavior, which is herein discussed, a rather efficient catalytic mechanism for the CO2 reduction reaction toward the generation of CO has been hypothesized.
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The Italian National Healthcare Service relies on per capita allocation for healthcare funds, despite having a highly detailed and wide range of data to potentially build a complex risk-adjustment formula. However, heterogeneity in data availability limits the development of a national model. This paper implements and ealuates machine learning (ML) and standard risk-adjustment models on different data scenarios that a Region or Country may face, to optimize information with the most predictive model. We show that ML achieves a small but generally statistically insignificant improvement of adjusted R2 and mean squared error with fine data granularity compared to linear regression, while in coarse granularity and poor range of variables scenario no differences were observed. The advantage of ML algorithms is greater in the coarse granularity and fair/rich range of variables set and limited with fine granularity scenarios. The inclusion of detailed morbidity- and pharmacy-based adjustors generally increases fit, although the trade-off of creating adverse economic incentives must be considered.
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Programas Nacionales de Salud , Ajuste de Riesgo , Algoritmos , Humanos , Italia , Modelos LinealesRESUMEN
BACKGROUND: The objective of this systematic review is to investigate changes in the epidemiology of major trauma presentations during the implementation of movement restriction measures to manage the first wave of the SARS-CoV-2 (COVID-19) pandemic. METHODS: A systematic search in six databases, as well as a search of grey literature was performed from January 2020 to August 2021. Estimates were pooled using random-effects meta-analysis. The certainty of evidence was rated according to the GRADE approach. The review is reported using both PRISMA guideline and the MOOSE checklist. RESULTS: In total, 35 studies involving 36,987 patients were included. The number of major trauma admissions overall decreased during social movement restrictions (-24%; p < 0.01; 95% CI [-0.31; -0.17]). A pooled analysis reported no evidence of a change in the severity of trauma admissions (OR:1.17; 95%CI [0.77, 1.79], I2 = 77%). There was no evidence for a change in mortality during the COVID-19 period (OR:0.94, 95%CI [0.80,1.11], I2 = 53%). There was a statistically significant reduction in motor vehicle trauma (OR:0.70; 95%CI [0.61, 0.81], I2 = 91%) and a statistically significant increase in admissions due to firearms and gunshot wounds (OR:1.34; 95%CI [1.11, 1.61], I2 = 73%) and suicide attempts and self-harm (OR:1.41; 95%CI [1.05, 1.89], I2 = 39%). CONCLUSIONS AND RELEVANCE: Although evidence continues to emerge, this systematic review reports some decrease in absolute major trauma volume with unchanged severity and mortality during the first wave of COVID-19 movement restriction policies. Current evidence does not support the reallocation of highly specialised trauma professionals and trauma resources. Registration PROSPERO ID CRD42020224827.
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COVID-19 , Heridas por Arma de Fuego , COVID-19/epidemiología , Hospitalización , Humanos , Políticas , SARS-CoV-2RESUMEN
Software Defined Networking represents a mature technology for the control of optical networks, though all open controller implementations present in the literature still lack the adequate level of maturity and completeness to be considered for (pre)-production network deployments. This work aims at experimenting on, assessing and discussing the use of the OneM2M open-source platform in the context of optical networks. Network elements and devices are implemented as IoT devices, and the control application is built on top of an OneM2M-compliant server. The work concretely addresses the scalability and flexibility performances of the proposed solution, accounting for the expected growth of optical networks. The two experiment scenarios show promising results and confirm that the OneM2M platform can be adopted in such a context, paving the way to other researches and studies.
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Two-dimensional fused aromatic networks (2Dâ FANs) have emerged as a highly versatile alternative to holey graphene. The synthesis of 2Dâ FANs with increasingly larger lattice dimensions will enable new application perspectives. However, the synthesis of larger analogues is mostly limited by lack of appropriate monomers and methods. Herein, we describe the synthesis, characterisation and properties of an expanded 2Dâ FAN with 90-ring hexagons, which exceed the largest 2Dâ FAN lattices reported to date.
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OBJECTIVE: To explore whether placebo surgery controlled trials achieve what they set out to do by investigating discrepancy between projected and actual design aspects of trials identified through systematic review methods. SUMMARY BACKGROUND: Interest in placebo surgery controlled trials is growing in response to concerns regarding unnecessary surgery and the societal cost of low-value healthcare. As questions about the justifiability of using placebo controls in surgery have been addressed, attention is now being paid to more practical concerns. METHODS: Six databases were searched from inception - May 2020 (MEDLINE, Embase, Emcare, APA PsycInfo, CINAHL, Cochrane Library). Placebo surgery controlled trials with a published protocol were included. Three authors extracted "projected" design aspects from protocols and "actual" design aspects from main findings papers. Absolute and relative difference between projected and actual design aspects were presented for each trial. Trials were grouped according to whether they met their target sample size ("completed") and were concluded in a timely fashion. Pairs of authors assessed risk of bias. RESULTS: Of 24 trials with data available to analyse; 3 were completed and concluded within target timeframe; 10 were completed and concluded outside the target timeline; 4 were completed without clear target timeframes; 2 were incomplete and concluded within the target framework; 5 were incomplete and concluded outside the target timeline. Trials which reached the recruitment target underestimated trial duration by 88% and number of recruitment sites by 87%. CONCLUSIONS: Trialists need to factor additional time and sites into future placebo surgery controlled trials. A robust reporting framework of projected and actual trial design is imperative for trialists to learn from their predecessors. REVIEW REGISTRATION: PROSPERO (CRD42019133296).
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Ensayos Clínicos Controlados como Asunto/métodos , Placebos , Procedimientos Quirúrgicos Operativos , HumanosRESUMEN
Electrochemiluminescence (ECL) is a powerful transduction technique that has rapidly gained importance as a powerful analytical technique. Since ECL is a surface-confined process, a comprehensive understanding of the generation of ECL signal at a nanometric distance from the electrode could lead to several highly promising applications. In this work, we explored the mechanism underlying ECL signal generation on the nanoscale using luminophore-reporter-modified DNA-based nanoswitches (i.e., molecular beacon) with different stem stabilities. ECL is generated according to the "oxidative-reduction" strategy using tri-n-propylamine (TPrA) as a coreactant and Ru(bpy)32+ as a luminophore. Our findings suggest that by tuning the stem stability of DNA nanoswitches we can activate different ECL mechanisms (direct and remote) and, under specific conditions, a "digital-like" association curve, i.e., with an extremely steep transition after the addition of increasing concentrations of DNA target, a large signal variation, and low preliminary analytical performance (LOD 22 nM for 1GC DNA-nanoswtich and 16 nM for 5GC DNA-nanoswitch). In particular, we were able to achieve higher signal gain (i.e., 10 times) with respect to the standard "signal-off" electrochemical readout. We demonstrated the copresence of two different ECL generation mechanisms on the nanoscale that open the way for the design of customized DNA devices for highly efficient dual-signal-output ratiometric-like ECL systems.
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ADN , Mediciones Luminiscentes , Electrodos , FotometríaRESUMEN
An electrogenerated chemiluminescence (ECL) system by in situ coreactant production, where Ru(bpy)32+ emission is generated at a boron-doped diamond (BDD) electrode, is presented. The system takes advantage of the unique properties of BDD to promote oxidation of carbonate (CO32-) into peroxydicarbonate (C2O62-), which further reacts with water to form hydrogen peroxide (H2O2), which acts as a coreactant for Ru(bpy)32+ ECL. Investigation of the mechanism reveals that ECL emission is triggered by the reduction of H2O2 to hydroxyl radicals (OHâ¢), which later react with the reduced Ru(bpy)3+ molecules to form excited states, followed by light emission. The ECL signal was found to increase with the concentration of CO32-; therefore, with the concentration of electrogenerated H2O2, although at the same time, higher concentrations of H2O2 can quench the ECL emission, resulting in a decrease in intensity. The carbonate concentration, pH, and oxidation parameters, such as potential and time, were optimized to find the best emission conditions.
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In this work, we quantify the electrogenerated chemiluminescence arising from the reaction of electrogenerated tris(bipyridine)ruthenium(iii) with hydroxyl ions, in terms of emission intensity and reaction rate. Different electrode materials (glassy carbon and boron-doped diamond) and different supporting electrolytes (perchlorate, phosphate, and carbonate) were investigated with pH variation. Relative quantification of the electrogenerated chemiluminescence was achieved using the Ru(bpy)32+/tri-n-propylamine system, taken as a reference, with relative emission as low as 600 and 230 times that observed at the same coreactant concentration and the same pH, respectively. The kinetics was investigated by foot of the wave analysis of cyclic voltammetry to measure the turnover frequency of the reaction.
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The combination of highly sensitive techniques such as electrochemiluminescence (ECL) with nanotechnology sparked new analytical applications, in particular for immunoassay-based detection systems. In this context, nanomaterials, particularly dye-doped silica nanoparticles (DDSNPs) are of high interest, since they can offer several advantages in terms of sensitivity and performance. In this work we synthesized two sets of monodispersed and biotinylated [Ru(bpy)3 ]2+ -doped silica nanoparticles, named bio-Triton@RuNP and bio-Igepal@RuNP, obtained following the reverse microemulsion method using two different types of nonionic surfactants. Controlling the synthetic procedures, we were able to obtain nanoparticles (NPs) offering highly intense signal, using tri-n-propylamine (TPrA) as coreactant, with bio-Triton@RuNps being more efficient than bio-Igepal@RuNP.
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Colorantes/química , Inmunoensayo , Nanopartículas/química , Compuestos Organometálicos/química , Dióxido de Silicio/química , Colorantes/síntesis química , Técnicas Electroquímicas , Humanos , Mediciones Luminiscentes , Estructura Molecular , Nanotecnología , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
Controlled nitrogen-doping is a powerful methodology to modify the properties of carbon nanostructures and produce functional materials for electrocatalysis, energy conversion and storage, and sensing, among others. Herein, we report a wall- and hybridisation-selective synthetic methodology to produce double-walled carbon nanotubes with an inner tube doped exclusively with graphitic sp2 -nitrogen atoms. Our measurements shed light on the fundamental properties of nitrogen-doped nanocarbons opening the door for developing their potential applications.