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bstract There is compelling evidence that the poles have shifted in the past, but this idea is dismissed as impossible by the scientific community on the assumption that the stabilizing effect of the equatorial bulge is so great that no conceivable force could make the Earth shifting on its axis, except for the collision with a planet-size body. In theory, however, a wide shift of the poles could be obtained simply by reshaping the equatorial bulge, a ring of matter that from about 15km at the equator decreases down to zero at the poles. At least 20% of this matter is made by water, which covers 2/3d of the whole Earth. A well-known physical law assures that free liquid surfaces create instability, thus Earth is an inherently unstable planet. Every displacement of water provokes a wobbling of the axis of rotation. An ocean wide tide or tsunami of hundreds of meters would displace the axis of some degrees, therefore the polar icecaps would rotate off-center developing a toppling torque. The shift would increasingly grow to the point of provoking the sudden rebound of the Earth’s mantle and in the end a reshaping of the equatorial bulge around a different axis of rotation. We can imagine more than one reason that in theory could provoke a tide of the required magnitude, but the most probable culprit should be the impact of a large asteroid. The analysis of the behaviour of a gyroscope subject to a disturbing torque provides a clear explanation of why and how the impulsive torque produced by the impact of an asteroid could trigger a process which in the end results in a shift of the poles.

Set up a lung SBRT end-to-end (e2e) test and perform a multicentre validation.A group of medical physicists from four hospitals and the Italian Institute of Ionizing Radiation Metrology designed the present e2e test. One sub-group set up the test, while another tested its feasibility and ease of use. A satisfaction questionnaire was used to collect user feedback. Each participating centre (PC) received the ADAM breathing phantom, a microDiamond detector and radiochromic films. Following the e2e protocol, each PC performed its standard internal procedure for simulating, planning, and irradiating the phantom. Each PC uploaded its planning and treatment delivery data in a shared Google Drive. A single centre analyzed all the data.The e2e test was successfully performed by all PCs. Participants' comments indicated that ADAM was well suited to the purpose and the protocol well described. All PCs performed the test in static and dynamic modes. The ratio between measured and planned point dose obtained by PC1, PC2, PC3, PC4 was: 0.99, 0.96, 1.01 and 1.01 (static track) and 0.99, 1.02, 1.01 and 0.94 (dynamic track). The gamma passing rates (3 % global, 3 mm) between planned and measured dose maps were 98.5 %, 94.0 %, 99.1 % and 94.0 % (static track) and 99.5 %, 96.5 %, 86.0 % and 94.5 % (dynamic track) for PC1, PC2, PC3 and PC4, respectively.An e2e test for lung SBRT has been proposed and tested in a multicentre framework. The results and user feedback prove the validity of the proposed e2e test.

Semiconductor quantum dots embedded in hybrid circular Bragg gratings are a promising platform for the efficient generation of nonclassical light. The scalable fabrication of multiple devices with similar performance is highly desirable for their practical use as sources of single and entangled photons, while the ability to operate at telecom wavelength is essential for their integration with the existing fiber infrastructure. In this work we combine the promising properties of broadband hybrid circular Bragg gratings with a membrane-transfer process performed on 3" wafer scale. We develop and study single-photon sources based on InAs/GaAs quantum dots emitting in the telecom O-band, demonstrating bright single-photon emission with Purcell factor > 5 and count rates up to 10 MHz. Furthermore, we address the question of reproducibility by benchmarking the performance of 10 devices covering a wide spectral range of 50 nm within the O-band.

No contexto econômico e empresarial no qual vivemos, caracterizado por diversas mudanças e avanços, principalmente no consumo, podemos perceber que negócios e empreendedores criativos e com propósito têm se consolidado. A moda é um dos mercados que tem apresentado tais mudanças evidenciadas por algumas marcas que apresentam a preocupação com questões de sustentabilidade e propósito. Este artigo tem como objetivo principal identificar a aplicabilidade e os usos dos conceitos de empreendedorismo, moda e propósito, a partir de um estudo de caso da marca Somos Numa. A metodologia utilizada é a descritiva, com o estudo de caso da marca. Os dados foram coletados através de entrevistas em profundidade com os proprietários e da análise documental.

Objetivo: analisar o panorama atual da produção científica (inter) nacional acerca da fragilidade física em idosos e a relação com atividade física e exercício físico. Método: revisão integrativa da literaturarealizada nos portais e base de dados: Biblioteca Virtual em Saúde, National Library of Medicine – Pubmed e Cochrane Library. Utilizou-se estratégia única em inglês para os descritores e as palavras-chave, e foram selecionados 46 artigos para compor o corpus da revisão integrativa. Os artigos selecionados também foram classificados quanto ao nível de evidência. Resultados: observou-se associação entre diminuição de atividade física e fragilidade em idosos. A diminuição de atividade física foi considerada preditora de fragilidade, por sua vez, a fragilidade pode mediar a diminuição de atividade física. O exercício físico previne e trata a fragilidade física em idosos. Conclusão: a atividade física / exercícios exercem forte influência na condição de fragilidade em idosos. A diminuição de atividade física interfere no agravamento da fragilidade, e a prática dos exercícios físicos é capaz de prevenir e reverter a fragilidade. Esta revisão integrativa da literatura contribui para fundamentar as práticas gerontológicas que visem o incentivo à atividade física e ao exercício físico frente aos benefícios na condição de fragilidade.

Computed tomography (CT)-guided percutaneous needle biopsy of the lung is a well-recognized and relatively safe diagnostic procedure for suspicious lung masses. Systemic air embolism (SAE) is a rare complication of transthoracic percutaneous lung biopsies. Herein, we present a case of an 81-year-old man who underwent CT-guided percutaneous needle biopsy of a suspicious nodule in the lower lobe of the right lung. Shortly after the procedure, the patient coughed up blood which prompted repeat CT imaging. He was found to have a massive cardiac air embolism. The patient became unresponsive and, despite resuscitation efforts, was pronounced dead. The pathophysiology, risk factors, clinical features, radiological evidence, and autopsy findings associated with SAE are discussed, which may, in light of the current literature, assist with the dilemma between assessing procedural complications and medical liability. Given the instances of SAE in the setting of long operative procedures despite careful technical execution, providing accurate and in-depth information, including procedure-related risks, even the rarest but potentially fatal ones, is recommended for informed consent to reduce medicolegal litigation issues.

Not available.

Recent work on interpretability has focused on concept-based explanations, where deep learning models are explained in terms of high-level units of information, referred to as concepts. Concept learning models, however, have been shown to be prone to encoding impurities in their representations, failing to fully capture meaningful features of their inputs. While concept learning lacks metrics to measure such phenomena, the field of disentanglement learning has explored the related notion of underlying factors of variation in the data, with plenty of metrics to measure the purity of such factors. In this paper, we show that such metrics are not appropriate for concept learning and propose novel metrics for evaluating the purity of concept representations in both approaches. We show the advantage of these metrics over existing ones and demonstrate their utility in evaluating the robustness of concept representations and interventions performed on them. In addition, we show their utility for benchmarking state-of-the-art methods from both families and find that, contrary to common assumptions, supervision alone may not be sufficient for pure concept representations., Comment: To appear at AAAI 2023

Objetivo: investigar a associação entre força de preensão manual e características sociodemográficas e clínicas de idosos condutores de veículos automotores. Método: estudo transversal, realizado em clínicas de medicina de tráfego na cidade de Curitiba/Paraná, com 421 idosos (≥ 60 anos). Realizou-se análise estatística pelo modelo de Regressão Logística e Teste de Wald, considerando intervalo de confiança de 95% e valores de p

Este estudo teve como objetivo identificar as etapas da ITIL que poderiam ser adicionadas aos normativos de projetos que se utilizam das boas práticas preconizadas pelo PMBOK, quando do desenvolvimento de sistemas de informação para uso interno nas instituições. O trabalho teve como locus o Ministério Público Federal, possuindo abordagem qualitativa do tipo pesquisa documental. Os dados foram organizados em blocos, seguindo as etapas do ciclo de vida de serviços recomendado pela ITIL, apurando o percentual de aderência dos projetos às boas práticas da biblioteca. Ao final, constatou-se o percentual de aderência entre 40% e 60% em todas as etapas da ITIL, apontando-se diversas oportunidades de melhorias.

Skilled movements result from a mixture of feedforward and feedback mechanisms conceptualized by internal models. These mechanisms subserve both motor execution and motor imagery. Current research suggests that imagery allows updating feedforward mechanisms, leading to better performance in familiar contexts. Does this still hold in radically new contexts? Here, we test this ability by asking participants to imagine swinging arm movements around shoulder in normal gravity condition and in microgravity in which studies showed that movements slow down. We timed several cycles of actual and imagined arm pendular movements in three groups of subjects during parabolic flight campaign. The first, control, group remained on the ground. The second group was exposed to microgravity but did not imagine movements inflight. The third group was exposed to microgravity and imagined movements inflight. All groups performed and imagined the movements before and after the flight. We predicted that a mere exposure to microgravity would induce changes in imagined movement duration. We found this held true for the group who imagined the movements, suggesting an update of internal representations of gravity. However, we did not find a similar effect in the group exposed to microgravity despite the fact that the participants lived the same gravitational variations as the first group. Overall, these results suggest that motor imagery contributes to update internal representations of the considered movement in unfamiliar environments, while a mere exposure proved to be insufficient.

International audience; The large and still increasing popularity of deep learning clashes with a major limit of neural network architectures, that consists in their lack of capability in providing human-understandable motivations of their decisions. In situations in which the machine is expected to support the decision of human experts, providing a comprehensible explanation is a feature of crucial importance. The language used to communicate the explanations must be formal enough to be implementable in a machine and friendly enough to be understandable by a wide audience. In this paper, we propose a general approach to Explainable Artificial Intelligence in the case of neural architectures, showing how a mindful design of the networks leads to a family of interpretable deep learning models called Logic Explained Networks (LENs). LENs only require their inputs to be human-understandable predicates, and they provide explanations in terms of simple First-Order Logic (FOL) formulas involving such predicates. LENs are general enough to cover a large number of scenarios. Amongst them, we consider the case in which LENs are directly used as special classifiers with the capability of being explainable, or when they act as additional networks with the role of creating the conditions for making a black-box classifier explainable by FOL formulas. Despite supervised learning problems are mostly emphasized, we also show that LENs can learn and provide explanations in unsupervised learning settings. Experimental results on several datasets and tasks show that LENs may yield better classifications than established white-box models, such as decision trees and Bayesian rule lists, while providing more compact and meaningful explanations.

Explainable AI (XAI) underwent a recent surge in research on concept extraction, focusing on extracting human-interpretable concepts from Deep Neural Networks. An important challenge facing concept extraction approaches is the difficulty of interpreting and evaluating discovered concepts, especially for complex tasks such as molecular property prediction. We address this challenge by presenting GCI: a (G)raph (C)oncept (I)nterpretation framework, used for quantitatively measuring alignment between concepts discovered from Graph Neural Networks (GNNs) and their corresponding human interpretations. GCI encodes concept interpretations as functions, which can be used to quantitatively measure the alignment between a given interpretation and concept definition. We demonstrate four applications of GCI: (i) quantitatively evaluating concept extractors, (ii) measuring alignment between concept extractors and human interpretations, (iii) measuring the completeness of interpretations with respect to an end task and (iv) a practical application of GCI to molecular property prediction, in which we demonstrate how to use chemical functional groups to explain GNNs trained on molecular property prediction tasks, and implement interpretations with a 0.76 AUCROC completeness score.

Deep learning methods are highly accurate, yet their opaque decision process prevents them from earning full human trust. Concept-based models aim to address this issue by learning tasks based on a set of human-understandable concepts. However, state-of-the-art concept-based models rely on high-dimensional concept embedding representations which lack a clear semantic meaning, thus questioning the interpretability of their decision process. To overcome this limitation, we propose the Deep Concept Reasoner (DCR), the first interpretable concept-based model that builds upon concept embeddings. In DCR, neural networks do not make task predictions directly, but they build syntactic rule structures using concept embeddings. DCR then executes these rules on meaningful concept truth degrees to provide a final interpretable and semantically-consistent prediction in a differentiable manner. Our experiments show that DCR: (i) improves up to +25% w.r.t. state-of-the-art interpretable concept-based models on challenging benchmarks (ii) discovers meaningful logic rules matching known ground truths even in the absence of concept supervision during training, and (iii), facilitates the generation of counterfactual examples providing the learnt rules as guidance.

The rise of Artificial Intelligence (AI) recently empowered researchers to investigate hard mathematical problems which eluded traditional approaches for decades. Yet, the use of AI in Universal Algebra (UA) -- one of the fields laying the foundations of modern mathematics -- is still completely unexplored. This work proposes the first use of AI to investigate UA's conjectures with an equivalent equational and topological characterization. While topological representations would enable the analysis of such properties using graph neural networks, the limited transparency and brittle explainability of these models hinder their straightforward use to empirically validate existing conjectures or to formulate new ones. To bridge these gaps, we propose a general algorithm generating AI-ready datasets based on UA's conjectures, and introduce a novel neural layer to build fully interpretable graph networks. The results of our experiments demonstrate that interpretable graph networks: (i) enhance interpretability without sacrificing task accuracy, (ii) strongly generalize when predicting universal algebra's properties, (iii) generate simple explanations that empirically validate existing conjectures, and (iv) identify subgraphs suggesting the formulation of novel conjectures.

This work explores the possibility of creating and controlling unconventional nonlinearities by periodic driving, in a broad class of systems described by the nonlinear Schr\"odinger equation (NLSE). By means of a parent quantum many-body description, we demonstrate that such driven systems are well captured by an effective NLSE with emergent nonlinearities, which can be finely controlled by tuning the driving sequence. We first consider a general class of two-mode nonlinear systems - relevant to optical Kerr cavities, waveguides and Bose-Einstein condensates - where we find an emergent four-wave mixing nonlinearity, which originates from pair-hopping processes in the parent quantum picture. Tuning this drive-induced nonlinearity is shown to modify the phase-space topology, which can be detected through relative population and phase measurements. We then couple individual (two-mode) dimers in view of designing extended lattice models with unconventional nonlinearities and controllable pair-hopping processes. Following this general dimerization construction, we obtain an effective lattice model with drive-induced interactions, whose ground-state exhibits orbital order, chiral currents and emergent magnetic fluxes through the spontaneous breaking of time-reversal symmetry. We analyze these intriguing properties both in the weakly-interacting (mean-field) regime, captured by the effective NLSE, and in the strongly-correlated quantum regime. Our general approach opens a route for the engineering of unconventional optical nonlinearities in photonic devices and controllable drive-induced interactions in ultracold quantum matter., Comment: 32 pages, 20 figures, including Appendices. Extended version of arXiv:2203.05554

Higher-order topological crystalline phases in low-dimensional interacting quantum systems represent a challenging and largely unexplored research topic. Here, we derive a Hamiltonian describing fermions interacting through correlated hopping processes that break chiral invariance, but preserve both inversion and time-reversal symmetries. In this way, we show that our one-dimensional model gives rise to an interacting second-order topological insulating phase that supports gapped edge states. The topological nature of such interacting phase turns out to be revealed by both long-range order of a non-local string correlation function and by even degeneracy of the entanglement spectrum. For strong interactions we instead find that the topological crystalline phase is destroyed and replaced by a singlet superconducting phase. The latter, characterized by local fermionic pairing, turns out to appear both in a homogeneous and in a phase separated form. Relevantly, the derived one-dimensional model and the second-order topological insulator can be explored and investigated in atomic quantum simulators., 4 pages, 3 figures, updated Refs

Objetivo: analisar as publicações científicas sobre a relação entre força de preensão manual, funcionalidade e fragilidade física em pessoas idosas. Método: revisão integrativa realizada nas bases de dados PubMed, CINAHL, Web of Science e Portal BVS, no período amostral de janeiro de 2010 a novembro de 2021. Empregou-se o fluxograma do Preferred Reporting Items for Systematic Reviews and Meta-analyses para apresentar a seleção dos estudos, e o nível de evidência foi avaliado a partir do Oxford Centre for Evidence-Based Medicine e as referências gerenciadas no EndNote Web. Resultados: a busca inicial resultou em 211 estudos após a aplicação dos critérios de elegibilidade, sendo que 7 estudos constituíram a revisão integrativa. A força de preensão manual se revelou um importante indicador de força muscular e crucial para a funcionalidade das pessoas idosas. Quando associada a determinadas ocorrências clínicas, a força de preensão manual colabora para a redução da funcionalidade e dependência na realização das atividades de vida diária em idosos, com maior prejuízo entre aqueles com 75 anos ou mais, de forma mais significativa entre as mulheres. Conclusão: a relação entre a força de preensão reduzida e a diminuição da funcionalidade determina a condição de fragilidade física em pessoas idosas. Isso reforça a importância do investimento dos profissionais de Enfermagem em intervenções que viabilizem a manutenção da força muscular e da funcionalidade e a reversão da fragilidade física nesse segmento populacional.

Gualaxo do Norte River (GNR), in southeastern Brazil, was impacted by iron ore tailings from the Fundão Dam rupture (November 2015). The deposition of tailings on the riverbed has changed the hydrogeomorphological characteristics of the GNR, resulting in a decrease in the diversity of physical habitats and the ecological biodiversity. As part of the process of restoration and management of this damaged ecosystem, the river restoration project ReNaturalize was implemented to restructure the geomorphological characteristics and the physical habitat, and to enhance the reestablishment of biota, mainly for macroinvertebrates and fishes. For this goal, 203 wooden structures, such as tree trunks, branches and grass were installed in two sections of GNR (T6R and T7R), totaling 1.8 km long. The effectiveness of the project was evaluated by an assessment that followed a before/after and control/impacted (BACI) design. Upstream of each Restored reach there is a Control and a Reference reach. Four campaigns were carried out, 2 before and 2 after the restoration process. After 14 months of the woody installation, an increase in hydraulic retention in the restored reaches was observed (T6R-20.2%; T7R-63.5%), when compared to the control reaches, which favored the accumulation of sediments (T6R-388 metric tons; T7R-396 metric tons). This enhanced the formation of natural tailings barriers and promoted enrichment of substrate types (T6R-39.2%; T7R-43%). The benthic macroinvertebrate community showed an increase in the total abundance (T6 - 110%), including the most sensitive groups (T6R-124%; T7R-124%). For fish, the increase was up to 81.38% with hand nets capture, indicating recruitment of juveniles; and the abundance and the biomass of some species were also higher (up to 100%) than the Control reaches. The results indicated that the Restored reach is already qualitatively and quantitatively better than Control reach and similar to the Reference reach, indicating the success of the study. This article is protected by copyright. All rights reserved. Integr Environ Assess Manag 2022;00:0-0. © 2022 SETAC.

The letters in Plautus are potent tools for making and thinking about Plautine comedy inside Plautine comedy. Emilia Barbiero demonstrates that Plautus' embedded letters reify the internal performance and evince its theatricality by means of the epistolary medium's script-like ability to precipitate presence in absence. These missives thus serve as emblems of the dramatic script, and in their onstage composition and recitation they cast a portrait of the plays' textual origins into the plays themselves. But by virtue of their inscription with a premise which is identical to that of the comedies they inhabit, the Plautine letters also reproduce the relationship between the playwright's Greek models and his Latin translations: the mirror effect created by a dramatic text inscribed, read and realized within a dramatic text whose plot it also duplicates generates a mise-en-abyme which ultimately serves to contemplate problems of novelty and literary ownership that beset Plautus' literary endeavor.

Human-driven environmental change underlies recent changes in water clarity in many of the world’s great lakes, yet our understanding of the consequences of these changes on the fish and fisheries they support remains incomplete. Herein, we offer a framework to organize current knowledge, guide future research, and help fisheries managers understand how water clarity can affect their valued populations. Emphasizing Laurentian Great Lakes findings where possible, we describe how changing water clarity can directly affect fish populations and communities by altering exposure to ultraviolet radiation, foraging success, predation risk, reproductive behavior, or territoriality. We also discuss how changing water clarity can affect fisheries harvest and assessment through effects on fisher behavior and sampling efficiency (i.e., catchability). Finally, we discuss whether changing water clarity can affect understudied aspects of fishery performance, including economic and community benefits. We conclude by identifying generalized predictions and discuss their implications for priority research questions for the Laurentian Great Lakes. Even though the motivation for this work was regional, the breadth of the review and generality of the framework are readily transferable to other freshwater and marine habitats.

Background: Not being well controlled by therapy with inhaled corticosteroids and long-acting β2 agonist bronchodilators is a major concern for severe-asthma patients. Current treatment option for these patients is the use of biologicals such as anti-IgE treatment, omalizumab, as add-on therapy. Despite the accepted use of omalizumab, patients do not always benefit from it. Therefore, there is a need to identify reliable biomarkers as predictors of omalizumab response. Methods: Two novel computational algorithms, machine-learning based Recursive Ensemble Feature Selection (REFS) and rule-based algorithm Logic Explainable Networks (LEN ) were used on open accessible mRNA expression data from moderate-to-severe asthma patients to identify genes as predictors of omalizumab response Results: With REFS, the number of features were reduced from 28,402 genes to 5 genes while obtaining a cross-validated accuracy of 0.975. The 5 responsiveness predictive genes encode for the following proteins: Coiled-coil domain- containing protein 113 (CCDC113), Solute Carrier Family 26 Member 8 (SLC26A), Protein Phosphatase 1 Regulatory Subunit 3D (PPP1R3D), C-Type lectin Domain Family 4 member C (CLEC4C) and LOC100131780 (not annotated). The LEN algorithm found 4 identical genes with REFS: CCDC113 ,SLC26A8 PPP1R3D and LOC100131780. Literature research showed that the 4 identified responsiveness predicting genes are associated with: mucosal immunity, cell metabolism, and airway remodeling. Conclusion and clinical relevance: Both computational methods show 4 identical genes as predictors of omalizumab response in moderate-to-severe asthma patients. The obtained high accuracy indicates that our approach has potential for clinical settings. Future studies in relevant cohort data should validate our computational approach.

Parkinson's disease is a neurodegenerative disease, the etiology of which remains unknown, but some likely causes include oxidative stress, mitochondrial dysfunction and neuroinflammation. Peroxisome-proliferator-activated receptor (PPAR) agonists have been studied in animal models of Parkinson's disease and have shown neuroprotective effects. In this study, we aimed to (1) confirm the neuroprotective effects of PPAR-alpha agonist fenofibrate. To this end, male rats received fenofibrate (100 mg/kg) orally for 15 days, 5 days before the intraperitoneal injections of rotenone (2.5 mg/kg for 10 days). After finishing the treatment with rotenone and fenofibrate, animals were subjected to the open field, the forced swim test and the two-way active avoidance task. Subsequently, rats were euthanized for measurement of dopamine and metabolites levels in the striatum and quantification of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta (SNpc). In addition, we aimed to (2) evaluate the neuroprotective effects of fenofibrate on the accumulation of α-synuclein aggregates. Here, rats were treated for 5 days with fenofibrate continuing for over 28 days with rotenone. Then, animals were perfused for immunohistochemistry analysis of α-synuclein. The results showed that fenofibrate reduced depressive-like behavior and memory impairment induced by rotenone. Moreover, fenofibrate diminished the depletion of striatal dopamine and protected against dopaminergic neuronal death in the SNpc. Likewise, the administration of fenofibrate attenuated the aggregation of α-synuclein in the SNpc and striatum in the rotenone-lesioned rats. Our study confirmed that fenofibrate exerted neuroprotective effects because parkinsonian rats exhibited reduced behavioral, neurochemical and immunohistochemical changes, and importantly, a lower number of α-synuclein aggregates.

Background Obesity and overweight in childhood can increase the risk of developing cardiovascular disease throughout live. Objectives This study provides an update of a meta-analysis of randomized clinical trials (RCT) published in 2014, to assess the effects of physical activity interventions on preventing cardiovascular risk factors in childhood. Methods This update combines data from the previous search with new data obtained from June 2013 to June 2020. Searches were performed on PubMed, EMBASE and Cochrane CENTRAL. The RCTs enrolled used interventions with physical activity longer than six months in school children aged 6-12 years, and evaluated body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels. Data analysis was performed using a random-effects model and a P value

In many management science or economic applications, it is common to represent the key uncertain inputs as continuous random variables. However, when analytic techniques fail to provide a closed-form solution to a problem or when one needs to reduce the computational load, it is often necessary to resort to some problem-specific approximation technique or approximate each given continuous probability distribution by a discrete distribution. Many discretization methods have been proposed so far; in this work, we revise the most popular techniques, highlighting their strengths and weaknesses, and empirically investigate their performance through a comparative study applied to a well-known engineering problem, formulated as a stress–strength model, with the aim of weighting up their feasibility and accuracy in recovering the value of the reliability parameter, also with reference to the number of discrete points. The results overall reward a recently introduced method as the best performer, which derives the discrete approximation as the numerical solution of a constrained non-linear optimization, preserving the first two moments of the original distribution. This method provides more accurate results than an ad-hoc first-order approximation technique. However, it is the most computationally demanding as well and the computation time can get even larger than that required by Monte Carlo approximation if the number of discrete points exceeds a certain threshold.

Immune checkpoint inhibitors (ICIs) have emerged as a promising class of cancer immunotherapies. Neurotoxicities are uncommon, but often severe, and potentially fatal complications of ICIs, and clinical experience is limited. The aim of this study is to further define the clinical spectrum and outcome of ICI-mediated neurotoxicities. Patients with ICI-associated neurotoxicities were identified from retrospective review of the quality control database at a single institution. Data regarding demographics, medical history, clinical presentation, diagnosis, management and outcome were recorded. We identified 18 patients with neurotoxicity following ICI therapy with pembrolizumab, nivolumab, atezolizumab, or ipilimumab for a diverse set of malignancies. Neurotoxicities comprised central demyelinating disorder (28%), autoimmune encephalitis predominantly affecting the grey matter (17%), aseptic meningitis (6%), myasthenia gravis (MG) (17%) with concurrent myositis (6%), sensorimotor polyneuropathy (11%) and hypophysitis (17%). Median time to onset of neurotoxicities was 5 weeks (range 1–72). All patients discontinued ICIs and received steroids with additional immunomodulation required in 9 patients, resulting in improvement for 16 of 18 patients. Grade 3–4 neurotoxicity developed in 14 patients, of whom 6 had died at database closure. Grade 3–4 severity negatively impacted overall survival (OS) (p = 0.046). ICI-mediated neurotoxicities present early, are rapidly progressive and include a diverse phenotype affecting the CNS, PNS and neuroendocrine system. A high level of vigilance is warranted, as early diagnosis and targeted treatment can substantially prevent morbidity and mortality. Prospective clinical trials are warranted to assess optimized management of ICI-induced neurotoxicities.

Resumen Objetivo: Analizar la asociación entre la velocidad de la marcha y la cognición de adultos mayores que se encuentran en asistencia ambulatoria geriátrica y gerontológica. Materiales y método: Estudio cuantitativo transversal realizado con 407 adultos mayores (> 60 años) atendidos en el Centro Ambulatorio de Geriatría y Gerontología del municipio de Sao José dos Pinhais, Paraná (Brasil). La condición de fragilidad física se evaluó utilizando el fenotipo de fragilidad y el cribado cognitivo mediante el Mini-Mental State Examination y el test de fluencia verbal semántica. El análisis univariado se realizó mediante una prueba de chi-cuadrado con nivel de significación estadístico de p < 0,05. Resultados: Del total de participantes, se observaron 226 (55,5 %) adultos mayores prefrágiles, 238 (58,5 %) reportaron deterioro cognitivo, 90 (22 %) de la fluidez verbal semántica y 205 (50,4 %) presentaron velocidad de la marcha reducida, variable que registró una asociación significativa con el deterioro cognitivo (p = 0,003) y las alteraciones de la fluencia verbal semántica (p < 0,001). Conclusiones: Los resultados señalan la necesidad de implementar la evaluación de la velocidad de la marcha en adultos mayores como parte de la práctica clínica de geriatría y gerontología. Este componente revela un posible deterioro cognitivo y permite la realización de acciones que puedan perfeccionar el manejo de los cuidados ante la fragilidad física en adultos mayores. Resumo Objetivo: Analisar a associação entre a velocidade da marcha e a cognição de idosos em assistência ambula-torial de geriatria e gerontologia. Materiais e método: Estudo quantitativo transversal, realizado com 407 idosos (> 60 anos), atendidos no Ambulatório de Geriatria e Gerontologia, do município de São José dos Pinhais, Paraná, Brasil. A condição de fragilidade física foi avaliada mediante o fenótipo de fragilidade e o rastreio cognitivo pelo Mini-Exame do Estado Mental e Teste de Fluência Verbal Semântica. A análise univa-riada foi realizada por teste de qui-quadrado com nível de significância estatístico de p < 0,05. Resultados: Do total de participantes, foram observados 226 (55,5 %) idosos pré-frágeis, 238 (58,5 %) apresentaram declínio cognitivo, 90 (22 %) comprometimento na fluência verbal semântica e 205 (50,4 %) velocidade da marcha reduzida, variável que registrou associação significativa com o comprometimento cognitivo (p = 0,003) e alterações da fluência verbal semântica (p < 0,001). Conclusões: Os resultados apontam para a necessidade de implementar na prática clínica de geriatria e gerontologia a avaliação da velocidade da marcha em idosos. Esse componente revela possibilidades de comprometimento cognitivo e faculta ações que possam aprimorar a gestão de cuidados diante da fragilidade física em idosos. Abstract Objective: To study the association between gait speed and cognition in elderly patients undergoing geriatric and gerontological outpatient treatment. Materials and method: Quantitative and cross-sectional study with 407 elderly patients (a60 years) treated at the Geriatrics and Gerontology Outpatient Clinic in the town of São José dos Pinhais, Paraná (Brazil). Physical frailty condition was assessed using the frailty phenotype and the cognitive assessment by means of the Mini Mental State Examination and the Semantic Verbal Fluency Test. The univariate analysis was performed using a chi-square test with a level of statistical significance of p s 0.05. Results: Out of the total participants, we observed that 226 (55.5%) elderly patients were pre-frail, 238 (58.5%) had cognitive impairments, g0 (22%) showed impaired semantic verbal fluency, and 205 (50.4%) decreased gait speed. This last variable showed a significant association with cognitive decline (p = 0.003) and changes in semantic verbal fluency (p < 0.001). Conclusions: Our results indicate the need of implementing gait speed assessment in elderly patients in the geriatrics and gerontology clinical practice. This component reveals a possible cognitive deterioration and enables us to develop actions that may improve care management in the face of physical frailty in elderly individuals.

Canada spends more than Italy on health per capita and as a share of GDP and has a higher per capita GDP. Yet, life expectancy and infant mortality in Italy are better and have improved more over time. The implication is that the Italian health care system provides better value for money. We examine whether Italy does get better health outcomes at lower costs. Using regression analysis, we find that health spending is determined by similar drivers in both Canada and Italy. We also find that more social spending and health spending in either country do not satisfactorily explain the differences in health outcomes, suggesting the importance of broader socio-economic determinants like income and life-style choices. We conclude that while the levels of per capita health spending in Canada are higher than Italy, this partly reflects historical inertia in Canadian health spending partially attributable to the higher costs of health professionals relative to Italy.

A presente pesquisa tem o objetivo de fazer um paralelo entre os precedentes judiciais da common law e como estes são inseridos no contexto brasileiro. Para isso, faz-se uma análise dos elementos constitutivos e práticos dos precedentes judiciais no sistema common law, como também a perspectiva histórica que culminou seu surgimento. Ademais, verifica-se os novos enquadramentos judiciários e atividades do juiz a partir dessa nova lógica vinculante no direito processual brasileiro. O precedente se torna um instrumento adequado para resolver os problemas de duração dos processos judicias e segurança jurídica do judiciário, e sua efetividade só poderá ser medida com a sua prática.PALAVRAS-CHAVE:‌ Common law; Precedentes judiciais; Processo Civil.

This scientific work aims analyse judicial decisions about (in)constitutionality of municipal laws that prohibit the consuption of alcoholic beverages in public spaces. In this way is studied the historical evolution of fundamental rights, with emphasis on first generation rights, individual liberties, the legislative municipal autonomy, the fundamental rights restrictions and the decisions of the Santa Catarina and Parana Courts, based mainly on the principle of proportionality and its sub-elements. Theses judicial decisions points out the inconstitutionality of the municipal laws.