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Funding: Data collection was largely funded by the UK Natural Environment Research Council (NERC) project TREMOR (NE/N004655/1) to D.G., E.G. and O.P., with further funds from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES, finance code 001) to J.V.T. and a University of Leeds Climate Research Bursary Fund to J.V.T. D.G., E.G. and O.P. acknowledge further support from a NERC-funded consortium award (ARBOLES, NE/S011811/1). This paper is an outcome of J.V.T.’s doctoral thesis, which was sponsored by CAPES (GDE 99999.001293/2015-00). J.V.T. was previously supported by the NERC-funded ARBOLES project (NE/S011811/1) and is supported at present by the Swedish Research Council Vetenskapsrådet (grant no. 2019-03758 to R.M.). E.G., O.P. and D.G. acknowledge support from NERC-funded BIORED grant (NE/N012542/1). O.P. acknowledges support from an ERC Advanced Grant and a Royal Society Wolfson Research Merit Award. R.S.O. was supported by a CNPq productivity scholarship, the São Paulo Research Foundation (FAPESP-Microsoft 11/52072-0) and the US Department of Energy, project GoAmazon (FAPESP 2013/50531-2). M.M. acknowledges support from MINECO FUN2FUN (CGL2013-46808-R) and DRESS (CGL2017-89149-C2-1-R). C.S.-M., F.B.V. and P.R.L.B. were financed by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES, finance code 001). C.S.-M. received a scholarship from the Brazilian National Council for Scientific and Technological Development (CNPq 140353/2017-8) and CAPES (science without borders 88881.135316/2016-01). Y.M. acknowledges the Gordon and Betty Moore Foundation and ERC Advanced Investigator Grant (GEM-TRAITS, 321131) for supporting the Global Ecosystems Monitoring (GEM) network (gem.tropicalforests.ox.ac.uk), within which some of the field sites (KEN, TAM and ALP) are nested. The authors thank Brazil–USA Collaborative Research GoAmazon DOE-FAPESP-FAPEAM (FAPESP 2013/50533-5 to L.A.) and National Science Foundation (award DEB-1753973 to L. Alves). They thank Serrapilheira Serra-1709-18983 (to M.H.) and CNPq-PELD/POPA-441443/2016-8 (to L.G.) (P.I. Albertina Lima). They thank all the colleagues and grants mentioned elsewhere [8,36] that established, identified and measured the Amazon forest plots in the RAINFOR network analysed here. The authors particularly thank J. Lyod, S. Almeida, F. Brown, B. Vicenti, N. Silva and L. Alves. This work is an outcome approved Research Project no. 19 from ForestPlots.net, a collaborative initiative developed at the University of Leeds that unites researchers and the monitoring of their permanent plots from the world’s tropical forests [61]. The authros thank A. Levesley, K. Melgaço Ladvocat and G. Pickavance for ForestPlots.net management. They thank Y. Wang and J. Baker, respectively, for their help with the map and with the climatic data. The authors acknowledge the invaluable help of M. Brum for kindly providing the comparison of vulnerability curves based on PAD and on PLC shown in this manuscript. They thank J. Martinez-Vilalta for his comments on an early version of this manuscript. The authors also thank V. Hilares and the Asociación para la Investigación y Desarrollo Integral (AIDER, Puerto Maldonado, Peru); V. Saldaña and Instituto de Investigaciones de la Amazonía Peruana (IIAP) for local field campaign support in Peru; E. Chavez and Noel Kempff Natural History Museum for local field campaign support in Bolivia; ICMBio, INPA/NAPPA/LBA COOMFLONA (Cooperativa mista da Flona Tapajós) and T. I. Bragança-Marituba for the research support. Tropical forests face increasing climate risk1,2, yet our ability to predict their response to climate change is limited by poor understanding of their resistance to water stress. Although xylem embolism resistance thresholds (for example, Ψ50) and hydraulic safety margins (for example, HSM50) are important predictors of drought-induced mortality risk3-5, little is known about how these vary across Earth's largest tropical forest. Here, we present a pan-Amazon, fully standardized hydraulic traits dataset and use it to assess regional variation in drought sensitivity and hydraulic trait ability to predict species distributions and long-term forest biomass accumulation. Parameters Ψ50 and HSM50 vary markedly across the Amazon and are related to average long-term rainfall characteristics. Both Ψ50 and HSM50 influence the biogeographical distribution of Amazon tree species. However, HSM50 was the only significant predictor of observed decadal-scale changes in forest biomass. Old-growth forests with wide HSM50 are gaining more biomass than are low HSM50 forests. We propose that this may be associated with a growth-mortality trade-off whereby trees in forests consisting of fast-growing species take greater hydraulic risks and face greater mortality risk. Moreover, in regions of more pronounced climatic change, we find evidence that forests are losing biomass, suggesting that species in these regions may be operating beyond their hydraulic limits. Continued climate change is likely to further reduce HSM50 in the Amazon6,7, with strong implications for the Amazon carbon sink. Publisher PDF

PurposeThe present paper aims at understanding how horizontal network collaborations between small and medium enterprises (SMEs) can be designed and implemented to take advantage of a supply chain finance (SCF) perspective.Design/methodology/approachThis study presents an SCF literature background identifying four literature gaps, and in response to them it adopts an action research approach. The empirical analysis is developed on a network-case study: a horizontal collaboration project between small businesses of the Italian wine industry and their supply chains.FindingsSMEs can play an active role in developing – in terms of design and implementation – their collaborative networks by taking advantage of an SCF perspective for themselves, and their customers, based on the reorganization of relationships interface processes. Taking this perspective can be a concrete and crucial way to sustain the development of SMEs and their supply chains in an actual competitive context.Research limitations/implicationsThe paper identifies the theoretical gaps in the literature, suggests new research areas that deserve to be more deeply investigated and connects case-related results to the key concepts. The empirical part presents a real case application that proposes a complete roadmap for managers and practitioners who wish to experience similar projects.Practical implicationsThis network-case study storyline, presenting an overview of ten years of meetings, with related purposes, is suggesting a roadmap for design and implementation of horizontal network as managerial implications. These kinds of active research projects, with a collaborative mixed team of academics and practitioners, and involving a multilayer group of participants, are positive examples for closing the bridge between companies and academia, which enhance this network of small businesses active in trying to improve their competitiveness working together.Originality/valueThe value of the paper is to embrace a supply chain-oriented perspective for an SME, independent of the financial system and based on inventory flow management. Very little literature focuses on inventory-based research within the SCF framework, designed for real implementation in horizontal network collaboration by entrepreneurial ventures.

Construction is hard work which involves many elements, from the use of heavy equipment to the involvement of large amounts of materials. This causes the world of construction to have a higher risk of work accidents compared to other types of work. For this reason, all parties must understand the importance of implementing Occupational Safety and Health (K3) in construction projects. Socialization of the application of K3 was carried out including the bridge project on Jalan Bilal, Medan. The service will be held on January 16 2023 at 11.00 – 13.00 WIB with the lecture and discussion method. In the early stages, the speaker gave a lecture by introducing the types of personal protective equipment and the importance of applying K3. Then a discussion was held, where the presenter gave the opportunity to the participants to ask questions about K3. In-depth knowledge of OSH and awareness of workers to implement OSH is the result to be achieved in this service

Introdução: o termo de consentimento informado (TCI) é um documento ético que tem a função de informar o paciente acerca de determinado procedimento, permitindo que ele possa exercer seu direito de livre autonomia. Não obstante, poucos médicos recebem formação para utilizar o TCI, o que gera um paradoxo visto sua importância no contexto médico e legal. Objetivo: mapear informações a respeito do TCI e sua aplicabilidade no cenário atual. Método: Trata-se de uma revisão de escopo, técnica de análise que permite mapear o conhecimento acerca de determinado tema, possibilitando assim obter um cenário amplo acerca do tema pesquisado. Resultados: Os estudos demonstraram que os médicos reconhecem a importância desse documento na relação médico-paciente e na tomada de decisão compartilhada, entretanto, uma pequena parcela desse grupo acredita que o paciente não tem entendimento suficiente para intervir diretamente sobre sua saúde. Além disso, observou-se um déficit em sua obtenção por falha de comunicação. Conclusão: Observa-se visível presença de lacunas durante a formação acadêmica, com repercussão direta na prática médica, onde muitos médicos se sentem inseguros e despreparados para obter esse documento.

Immune checkpoint inhibitors have significantly improved the therapeutic scenario of many different advanced malignancies and could be an effective treatment strategy in synchronous or metachronous tumors. The authors describe the clinical case of a patient who experienced a long-lasting response of his metastatic renal cell carcinoma and an optimal response of his locally advanced cutaneous squamous cell carcinoma to immunotherapy. The systemic treatment was chosen based on a literature review of several clinical reports, since there was no prospective study on anti-PD-1 blockade activity in cutaneous squamous cell carcinoma when the patient started the treatment. This clinical case supports the growing evidence for immunotherapy as a valid treatment option across different types of advanced tumors.Immunotherapy is an effective treatment strategy across different cancer types and could be a valid treatment strategy in patients with multiple malignant tumors. In this scenario, in fact, the main challenge is to choose a systemic treatment which could be active on both tumors with an acceptable toxicity profile. The authors report the clinical case of a patient with metastatic renal cell carcinoma and a disfiguring cutaneous cancer of the zygomatic region who experienced a durable response of the renal tumor and almost a complete clinical response of the cutaneous cancer.

Background and purpose: Real-world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease-modifying therapies (DMTs). Our aim was to provide real-world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab. Methods: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation. Results: We studied 322 patients (mean age 36.8years, median EDSS score 3, median follow-up 1.94years). Previous treatments were: fingolimod (106), natalizumab (80), first-line oral agents (56), first-line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty-five patients were treatment-naïve. The pre-alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p&nbsp

O processo carioso pode provocar alterações morfológicas e funcionais, sendo o Streptoccus muttans um dos microrganismos mais comuns devido a sua capacidade de aderência sobre a superfície da estrutura dentária. Os danos causados podem ser recuperados a partir de técnicas restauradoras do elemento dental. Estudos têm demostrado que o uso de protocolos de polimento e acabamento torna a superfície mais lisa, dificultando a adesão microbiana e, consequentemente, recidivas. Logo, o objetivo deste estudo foi avaliar in vitro, a influência do uso das tiras Sof-Lex na adesão bacteriana aos materiais restauradores Z100 e Z250. Para realização do estudo, foram confeccionados 24 espécimes (N=6), que foram divididos em dois grupos com protocolos de polimento (G1 e G3) e dois sem protocolos de polimento (G2 e G4), os grupos permaneceram em frascos contendo meio de cultura inoculado com Streptococcus muttans para a adesão microbiana. Após o período de incubação, os espécimes foram trocados de frasco contendo solução salina, agitados em vórtex, diluídos sequencialmente e plaqueados em meio de cultura para realização da contagem das UFC. Os dados dos diferentes grupos foram submetidos ao teste Kruskal-Wallis One Way Analysis of Variance e o nível de significância foi de 5%. Os resultados mostram que não houve diferença estatística entre os tipos de resinas avaliados, porém ambas apresentaram menor aderência microbiana quando submetidas ao polimento. Diante dos resultados, podemos concluir que o polimento das resinas compostas reduz o risco de formação do biofilme sobre a superfície do material. IN VITRO EVALUATION OF THE INFLUENCE OF POLISHING PROTOCOLS ON BACTERIAL ADHESION ON COMPOSITE RESIN ABSTRACT The carious disease process may cause morphological and functional alterations, and Streptoccus muttans is one of the most common microorganisms due to its capacity of adherence on the surface of the dental structure. The damage caused may be repaired with restorative techniques for the dental element. Studies have shown that the use of polishing and finishing protocols improves the smoothness of the surface, hindering microbial adhesion and, consequently, relapse. Therefore, the aim of this study was to evaluate in vitro, the influence of the use of Sof-Lex strips on bacterial adhesion to Z100 and Z250 restorative materials. To conduct the study, 24 specimens (N=6) were made and divided into two groups with polishing protocols (G1 and G3) and two with non-polishing protocols (G2 and G4), the groups remained in bottles containing culture medium inoculated with Streptococcus muttans for microbial adhesion. After the incubation period, the specimens were changed in bottles containing saline solution, vortexed, sequentially diluted, and plated in culture medium for CFU counting. The data from the different groups were submitted to the Kruskal-Wallis One Way Analysis of Variance test and the significance level was 5%. The results obtained demonstrated that there was no statistical difference between the types of resins evaluated, although both of them presented less microbial adherence when submitted to polishing. Given the results, we can conclude that the polishing of composite resins reduces the risk of biofilm formation on the surface of the material. Keywords: Operative Dentistry. Dental Polishing. Composite resins. Streptococcus mutans.

Este trabalho aborda, a partir de outros autores, a questão do território, e da territorialidade, sob uma perspectiva que visa à autonomia. A discussão sobre essa categoria, nos auxilia na valorização da fala de uma moradora do bairro Euzébio Beltrão de Queiroz, na cidade de Caxias do Sul, que carrega a ousadia de imaginar um território, e, portanto, uma territorialidade outra, avessa ao discurso standardizado do planejamento urbano praticado pelo estado. Considera-se a importância do ousado exercício de imaginar outras dinâmicas espaciais, outras dinâmicas de vida. A fala da moradora nos chama para a construção de espacialidades outras.

Background: CO2 rebreathing is one of the risks associated with noninvasive ventilation (NIV), possibly contributing to failure. In a bench study, we showed that a novel mask design, with separate limbs for inflow and outflow gases, significantly reduced CO2 rebreathing in different ventilation settings. Objectives: The study aimed to test whether a new mask design could 1) reduce CO2 rebreathing in healthy volunteers during NIV (phase 1) and 2) reduce minute ventilation (phase 2). Materials and Methods: Healthy volunteers were randomly assigned to NIV using two masks in a crossover design: a traditional single-limb mask for inflow and outflow gases and a mask with two separated limbs. In phase 1, six ventilation settings were tested for each mask: CPAP (PEEP 5 cmH2O) and pressure support ventilation (PSV, PS Level 5 cmH2O) using a mechanical ventilator with a bias flow of 8 or 20 L/min; free-flow CPAP (PEEP 5 cmH2O) with 60 or 90 L/min of gas flow. A nasal cannula was inserted in one nostril of the volunteers and connected to a CO2 gas analyzer to measure CO2 during the respiratory cycle. In phase 2, volunteers underwent a prolonged time of ventilation in CPAP 90 L/min and PSV with 20 L/min of bias flow. During free-flow CPAP, electrical impedance tomography was used to record the change in impedance during tidal breathing and then estimate tidal volume. Results: Ten healthy adults were enrolled in phase 1, and 8 volunteers in phase 2. CO2 during inspiration was significantly lower in each setting with the two-limb versus the one-limb mask (p < 0.001). The maximum CO2 reduction was observed in the continuous-flow CPAP settings. EtCO2 was lower with the two-limb mask compared to the one-limb mask (p < 0.001). However, no difference in minute ventilation was observed between the two masks. Conclusion: The new mask design with two ports for inhaled and exhaled gases reduced the amount of CO2 rebreathing in all tested ventilation settings. The CO2 rebreathing reduction did not decrease minute ventilation in healthy volunteers.

T1 Magnetization Prepared Two Rapid Acquisition Gradient Echo (MP2RAGE) with compress sensing (CS) has been proposed as an improvement of the standard MPRAGE sequence with multiple advantages including reduced acquisition time needed to provide a quantitative 3D anatomical image coupled with T1-map. Here we investigated the agreement between FreeSurfer-derived volume measurements obtained from MPRAGE and CS MP2RAGE acquisitions.MPRAGE and CS MP2RAGE images of 37 subjects (14 patients with neurodegenerative disorders and 23 healthy controls) were acquired on a 3 T MR scanner and grey matter volumes were extracted using standard FreeSurfer parcellation. Lin's concordance correlation coefficient (Lin's CCC), Bland-Altman analysis, Passing-Bablok regression and DICE similarity coefficient were calculated to assess the agreement between the two.We found a good correspondence for most of the regions examined, with 93.5 % of them showing a mean DICE index0.70. Poorer results were found with Lin's CCC especially for subcortical labels across patients. The Bland-Altman analysis showed CS MP2RAGE tended to measure lower cortical volumes compared to MPRAGE but in most cases the difference wasn't statistically relevant. The Passing-Bablock regression indicated overall an absence of systematic constant and proportional bias when CS MP2RAGE was used instead of MPRAGE.We found a good concordance for volumes obtained from MPRAGE and CS MP2RAGE images using FreeSurfer, suggesting a possible role of CS MP2RAGE for structural analysis with significant advantages like shorter acquisition time and the possibility to simultaneously obtain quantitative T1-maps of the brain enriching the diagnostic power of this technique.

Buscar um urbanismo incorporado que reconheça os muitos sujeitos que habitam o espaço é quebrar o consenso do espetáculo urbano. No conjunto de forças que definem as localizações na cidade, são os grupos sociais excluídos que, na escassez, resistem ao se apropriar do espaço, tempo, obra e festa. Resistir é tensionar através do corpo. É desviar do esperado. O presente trabalho, a partir de outros autores, reflete sobre o papel de arquitetas(os) e urbanistas na (trans)formação dos espaços do cotidiano. Chama atenção a necessidade de uma forma de atuar mais sensível aos conflitos e as diferentes formas de viver a urbanidade. Olhar para as muitas cidades dentro de uma, observar os movimentos ordinários e os espaços menores dos praticantes de cidade é não deixar apagar o protagonismo das comunidades, vilas e favelas. Conclui-se que é no olhar atento às complexidades da vida que poderemos encontrar caminho para uma cidade outra.

Mild behavioral impairment (MBI) has been increasingly regarded as the neurobehavioral axis of predementia risk states, but a specific investigation of its detection as a potential marker of prodromal dementia in motor neuron diseases (MNDs) is still lacking. The aims of our study were therefore to explore MBI in MNDs both at onset and over the disease course, and to evaluate its relationship with baseline and longitudinal cognitive features.Sixty MND patients with cognitive/behavioral, mood, and motor examinations were recruited and followed longitudinally for up to 15 months. Associations between baseline MBI symptoms and clinical features were tested using the Spearman correlation coefficient. Based on longitudinal data, relative deltas of variation for each cognitive measure were generated, and linear regression models were then used to evaluate the role of baseline MBI symptoms in predicting longitudinal rates of cognitive decline.At disease onset, the most impaired MBI domain was affective/emotional dysregulation, followed by impulse dyscontrol, apathy, and social inappropriateness. Greater MBI symptoms correlated with more severe baseline motor, cognitive/behavioral, and mood disturbances (p values from0.001 to 0.05). Longitudinally, the greatest decline was observed in the affective/emotional dysregulation domain, followed by impulse dyscontrol, apathy, and social inappropriateness. Greater MBI symptoms at onset were significant predictors of more severe longitudinal cognitive decline in both amyotrophic lateral sclerosis (ALS)-specific and ALS-nonspecific functions (p values from0.001 to 0.03).MBI represents a valuable clinical marker of incident cognitive decline in MNDs, and its evaluation has good potential for detecting dementia in its preclinical/prodromal phase.

Predictive monitoring of two key properties of nanocellulose, aspect ratio and yield of nanofibrillation, would help manufacturers control and optimize production processes, given the uncertainty that still surrounds their influential factors. For that, 20 different types of cellulosic and lignocellulosic micro/nanofibers produced from spruce and pine softwoods, and by different pre-treatment and fibrillation techniques, were used as training and testing datasets aiming at the development and evaluation of three machine learning models. The models used were Random Forests (RF), Linear Regression (LR) and Artificial Neural Networks (ANN), broadening the scope of our previous work (Santos et al. in Cellulose 29:5609–5622, 2022. https://doi.org/10.1007/s10570-022-04631-5). Performance of these models were evaluated by comparing statistical parameters such as Mean Absolute Percentage Error (MAPE) and R². For the aspect ratio and the yield of nanofibrillation, inputs were chosen among these easily controlled or measured variables: Total lignin (wt%), Cellulose (wt%), Hemicellulose (wt%), Extractives (wt%), HPH Energy Consumption (kWh/kg), Cationic Demand (µeq/g), Transmittance at 600 nm and Consistency index (Ostwald-De Waele’s k). In both cases, the ANN models trained here provided satisfactory estimates of aspect ratio (MAPE = 4.54% and R2 = 0.96) and the yield of nanofibrillation (MAPE = 6.74% and R2 = 0.98), being able to capture the effect of the applied energy along the fibrillation process. RF and LR models resulted in correlation coefficients of 0.93 and 0.95, respectively, for aspect ratio, while for yield of nanofibrillation the correlation coefficients were 0.87 and 0.92. The present work has been funded by the Spanish Ministry of Science and Innovation, projects CON-FUTURO-ES (PID2020-113850RBC22) and VALORCON-NC (PDC2021-120964-C22). Alexandre Ferreira Santos received funding from the Conselho Nacional de Desenvolvimento Científco e Tecnológico (CNPq, Brazil) for his research stay at University of Girona. The Human Resources Program of the National Agency of Petroleum, Natural Gas and Biofuels (PRH-ANP/Finep) from Brazil has economically supported the grant of Giovana S. Iamin. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.

Consular participation in state surveillance did not seem to be the basis of the legitimacy of Venetian consuls in Izmir in the late seventeenth and early eighteenth centuries. Indeed, their activity as informants did not contribute to producing the knowledge that was then used by those in power to make decisions, or to judge and punish illegal behaviour. By placing the Izmir consuls in a broader context in which the state rewarded the participation in a set of specific tasks of as many private individuals as possible, this article reassesses the oftendebated and much-contested efficacy of consular information activity. Rather than providing the Venetian authorities with reliable and indispensable information, this article argues that consular vigilance defined a bond of loyalty and mutual expectations between these consuls and Venice. Far from resulting in superior central control, political power projected its authority onto the narratives and behaviour of consuls and potential informers.

We study the Dirac decomposition of the gauge invariant quark propagator, whose imaginary part describes the hadronization of a quark as this interacts with the vacuum, and relate each of its coefficients to a specific sum rule for the chiral-odd and chiral-even quark spectral functions. Working at first in light-like axial gauge, we obtain a new sum rule for the spectral function associated to the gauge fixing vector, and show that its second moment is in fact equal to zero. Then, we demonstrate that the first moment of the chiral-odd quark spectral function is equal in any gauge to the so-called inclusive jet mass, which is related to the mass of the particles produced in the hadronization of a quark. Finally, we present a gauge-dependent formula that connects the second moment of the chiral-even quark spectral function to invariant mass generation and final state rescattering in the hadronization of a quark., 16 pages

Florentin Briffaz, Prunelle Deleville (dir.), Faire famille au Moyen Âge, Lyon (CIHAM-Éditions) 2022, 190 p. (Mondes médiévaux, 7), ISBN 978-2-9568426-6-8, EUR 25,00., Francia-Recensio, 2023/2

Objectives: Ankle sprains represent the second most common cause of emergency department access for musculoskeletal injury and lateral ankle ligament complex tears account for 850,000 cases annually in the United States with a relapse rate of 70%. Clinical examination is limited due to its subjectivity and the difficulty of identifying a specific involvement of the ligament; therefore, US and MRI are frequently requested. Therefore, the goal of this study is to analyze the available literature on the use of ultrasound (US) and magnetic resonance imaging (MRI) to diagnose injuries to the anterior talofibular ligament (ATFL) with a meta-analytic approach. Methods: According to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, all studies regarding the diagnostic accuracy of ultrasound and magnetic resonance imaging ATFL injuries were searched and assessed. The data were obtained from two independent reviewers with 12 and 3 years of experience in meta-analysis. A QUADAS-2 (Quality Assessment of Studies of Diagnostic Accuracy Studies) checklist was carried out to assess the risk of biases. From the selected studies, the sensitivity, specificity, and accuracy data were extracted. Results: Nine studies were included. The results of the meta-analysis demonstrate a greater sensitivity for ultrasound [96.88 (95% CI: 94–99) (fixed effects); 97 (95% CI: 94–99) (random effects)] compared to MRI [88.50 (95% CI: 85–91) (fixed effects); 86.98 (95% CI: 77–94) (random effects)], p < 0.05. The result of this meta-analysis shows that the less expensive diagnostic technique is also the most sensitive for the diagnosis of ATFL tears. Ultrasound articles resulted to have non-heterogeneity [(p = 0.2816; I° = 21.4607%)]. Conclusion: This meta-analysis demonstrates that US appears to be a highly sensitive diagnostic technique for diagnosing tears of the ATFL. Compared to MRI, the sensitivity of US result was higher.

This document presents the initial scientific case for upgrading the Continuous Electron Beam Accelerator Facility (CEBAF) at Jefferson Lab (JLab) to 22 GeV. It is the result of a community effort, incorporating insights from a series of workshops conducted between March 2022 and April 2023. With a track record of over 25 years in delivering the world's most intense and precise multi-GeV electron beams, CEBAF's potential for a higher energy upgrade presents a unique opportunity for an innovative nuclear physics program, which seamlessly integrates a rich historical background with a promising future. The proposed physics program encompass a diverse range of investigations centered around the nonperturbative dynamics inherent in hadron structure and the exploration of strongly interacting systems. It builds upon the exceptional capabilities of CEBAF in high-luminosity operations, the availability of existing or planned Hall equipment, and recent advancements in accelerator technology. The proposed program cover various scientific topics, including Hadron Spectroscopy, Partonic Structure and Spin, Hadronization and Transverse Momentum, Spatial Structure, Mechanical Properties, Form Factors and Emergent Hadron Mass, Hadron-Quark Transition, and Nuclear Dynamics at Extreme Conditions, as well as QCD Confinement and Fundamental Symmetries. Each topic highlights the key measurements achievable at a 22 GeV CEBAF accelerator. Furthermore, this document outlines the significant physics outcomes and unique aspects of these programs that distinguish them from other existing or planned facilities. In summary, this document provides an exciting rationale for the energy upgrade of CEBAF to 22 GeV, outlining the transformative scientific potential that lies within reach, and the remarkable opportunities it offers for advancing our understanding of hadron physics and related fundamental phenomena.

Background and purpose: Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation. Method: Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number. Results: From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p=0.005) and more in smoker patients (OR 1.39; p=0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p=0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p=0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p=0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p=0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p=0.024), joint or muscle pain (G2, p=0.013) and ageusia and anosmia (G5, p < 0.001). All cases should be referred to variants up to Delta. Conclusion: Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID-19 symptoms.

Background: CO2 rebreathing is one of the risks associated with noninvasive ventilation (NIV), possibly contributing to failure. In a bench study, we showed that a novel mask design, with separate limbs for inflow and outflow gases, significantly reduced CO2 rebreathing in different ventilation settings. Objectives: The study aimed to test whether a new mask design could 1) reduce CO2 rebreathing in healthy volunteers during NIV (phase 1) and 2) reduce minute ventilation (phase 2). Materials and Methods: Healthy volunteers were randomly assigned to NIV using two masks in a crossover design: a traditional single-limb mask for inflow and outflow gases and a mask with two separated limbs. In phase 1, six ventilation settings were tested for each mask: CPAP (PEEP 5 cmH2O) and pressure support ventilation (PSV, PS Level 5 cmH2O) using a mechanical ventilator with a bias flow of 8 or 20 L/min; free-flow CPAP (PEEP 5 cmH2O) with 60 or 90 L/min of gas flow. A nasal cannula was inserted in one nostril of the volunteers and connected to a CO2 gas analyzer to measure CO2 during the respiratory cycle. In phase 2, volunteers underwent a prolonged time of ventilation in CPAP 90 L/min and PSV with 20 L/min of bias flow. During free-flow CPAP, electrical impedance tomography was used to record the change in impedance during tidal breathing and then estimate tidal volume. Results: Ten healthy adults were enrolled in phase 1, and 8 volunteers in phase 2. CO2 during inspiration was significantly lower in each setting with the two-limb versus the one-limb mask (p < 0.001). The maximum CO2 reduction was observed in the continuous-flow CPAP settings. EtCO2 was lower with the two-limb mask compared to the one-limb mask (p < 0.001). However, no difference in minute ventilation was observed between the two masks. Conclusion: The new mask design with two ports for inhaled and exhaled gases reduced the amount of CO2 rebreathing in all tested ventilation settings. The CO2 rebreathing reduction did not decrease minute ventilation in healthy volunteers.

Background and objectives: alemtuzumab is a monoclonal anti-CD52 antibody acting on B and T cells in highly active multiple sclerosis (MS). We analyzed changes in lymphocyte subsets after alemtuzumab administration in relation to disease activity and autoimmune adverse events. Methods: lymphocyte subset counts were assessed longitudinally using linear mixed models. Subset counts at baseline and during follow-up were correlated with relapse rate, adverse events, or magnetic resonance (MRI) activity. Results: we recruited 150 patients followed for a median of 2.7 years (IQR: 1.9–3.7). Total lymphocytes, CD4, CD8, and CD20 significantly decreased in all patients over 2 years (p < 0.001). Previous treatment with fingolimod increased the risk of disease activity and adverse events (p = 0.029). We found a higher probability of disease reactivation in males and in patients with over three active lesions at baseline. Higher EDSS scores at baseline and longer disease duration predicted the switch to other treatments after alemtuzumab. Discussion and conclusions: Our real-world study supports data from clinical trials in which lymphocyte subsets were not useful for predicting disease activity or autoimmune disease during treatment. The early use of an induction therapy such as alemtuzumab in patients with a lower EDSS score and short history of disease could mitigate the risk of treatment failure.

Introduction: The diagnosis of the progression phase of Multiple Sclerosis (MS) is still retrospective and based on the objectivation of clinical disability accumulation. Objectives: To assess whether the Patient Reported Outcomes Measures (PROMs) scores predict the occurrence of disease progression within three years of follow-up. Methods: Observational prospective multicenter study. Stable Relapsing-Remitting MS (RRMS) patients were enrolled. At enrollment, patients completed the following PROMs: Beck Depression Inventory- II, The Treatment Satisfaction Questionnaire for Medications, Medical Outcomes Study Short Form 36- Item (SF36), Fatigue Severity Scale. EDSS was assessed at enrollment and three years later. The outcome measure was defined as the occurrence of confirmed disability progression (CDP) within three years of follow-up. Univariable and multivariable logistic regression models were performed to study the association between the final score of each test and the outcome. Results: SF36-Physical Functioning (SF36-PF) was the only independent variable associated with the outcome. The ROC curve analysis determined a score of 77.5 at SF36-PF as the cut-off point identifying patients experiencing CDP within three years of follow-up [AUC: 0.66 (95% CI: 0.56-0.75)]. Conclusions: RRMS patients scoring higher (>77.5) at SF36-PF subscale have a higher likelihood to experience CDP within the next three years.

The objective of this work was to evaluate the competitive ability of carioca bean cultivars BRS FC104, BRS FC402, IAC Imperador, IAC Milênio, IPR Tangará, and SCS Riqueza in the presence of Alexandergrass (Urochloa plantaginea) in different proportions of plants in association. The experiments were carried out in a greenhouse in a completely randomized design with four replications. The treatments were arranged according to the proportions of beans and Alexandergrass plants: 100:0, 75:25, 50:50, 25:75, and 0:100 or 40:00, 30:10, 20:20, 10:30, and 0:40 plants per pot. The competitiveness of the species was analyzed using diagrams applied to replacement experiments and also through relative competitiveness indices. At 30 days after crop emergence, leaf area (LA), height (HP), diameter (DP), and shoot dry mass (SM) of the plant shoots were measured, as well as variables related to the physiology of the species. There was competition among carioca bean cultivars in the presence of Alexandergrass regardless of the proportion of plants, causing decreases in DP, LA and SM. Basically, there is competition for the same environmental resources between beans and Alexandergrass. Highlights: There is competition between bean and Alexandergrass, for the same environmental resources; There is varietal difference - IAC Imperador and SCS 205 Riqueza are the most competitive ones; The escape to competition is the best approach to guarantee yield in Alexandergrass-infested fields.

Background and purpose Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID‐19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID‐19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID‐19 severity amongst PwMS. Methods Data were retrieved from an Italian web‐based platform (MuSC‐19) which includes PwMS with COVID‐19. PM2.5 2016–2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID‐19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID‐19 severity. Results In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID‐19 course (odds ratio 1.90; p = 0.009). Conclusions Even if several other factors explain the unfavourable course of COVID‐19 in PwMS, the role of air pollutants must be considered and further investigated., Air pollution, often assessed by particulate matter with diameter below 2.5 µg/m3, may contribute to severe COVID‐19 courses. 1087 patients were included, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died. Even if several other factors explain the unfavourable course of COVID‐19 in patients with multiple sclerosis, the role of air pollutants must be considered and further investigated.

BackgroundThe Spinnaker study evaluated survival outcomes and prognostic factors in patients with advanced non-small-cell lung cancer receiving first-line chemoimmunotherapy in the real world. This sub-analysis assessed the immunotherapy-related adverse effects (irAEs) seen in this cohort, their impact on overall survival (OS) and progression-free survival (PFS), and related clinical factors.MethodsThe Spinnaker study was a retrospective multicentre observational cohort study of patients treated with first-line pembrolizumab plus platinum-based chemotherapy in six United Kingdom and one Swiss oncology centres. Data were collected on patient characteristics, survival outcomes, frequency and severity of irAEs, and peripheral immune-inflammatory blood markers, including the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII).ResultsA total of 308 patients were included; 132 (43%) experienced any grade irAE, 100 (32%) Grade 1–2, and 49 (16%) Grade 3–4 irAEs. The median OS in patients with any grade irAES was significantly longer (17.5 months [95% CI, 13.4–21.6 months]) than those without (10.1 months [95% CI, 8.3–12.0 months]) (pConclusionsThese results confirm survival outcome benefits in patients with irAEs and suggest a higher likelihood of Grade 1–2 irAEs in patients with lower NLR or SII values or according to the NHS-Lung score.

In this contribution, we study an optimal control problem for the celebrated nonlocal Cahn-Hilliard equation endowed with the singular Flory-Huggins potential in the three-dimensional setting. The control enters the governing state system in a nonlinear fashion in the form of a prescribed solenoidal, that is a divergence-free, vector field, whereas the cost functional to be minimized is of tracking-type. The novelties of the present paper are twofold: in addition to the control application, the intrinsic difficulties of the optimization problem forced us to first establish new regularity results on the nonlocal Cahn-Hilliard equation that were unknown even without the coupling with a velocity field and are therefore of independent interest. This happens to be shown using the recently proved separation property along with ad hoc H\"older regularities and a bootstrap method. For the control problem, the existence of an optimal strategy as well as first-order necessary conditions are then established.

We aimed to evaluate the outcome of the disappearance or small remnants of colorectal liver metastases during first-line chemotherapy assessed by hepatobiliary contrast-enhanced and diffusion-weighted MR imaging (DW-MRI). Consecutive patients with at least one disappearing liver metastasis (DLM) or small residual liver metastases (≤10 mm) assessed by hepatobiliary contrast-enhanced and DW-MRI during first-line chemotherapy were included. Liver lesions were categorized into three groups: DLM; residual tiny liver metastases (RTLM) when ≤5 mm; small residual liver metastases (SRLM) when >5mm and ≤10 mm. The outcome of resected liver metastases was assessed in terms of pathological response, whereas lesions left in situ were evaluated in terms of local relapse or progression. Fifty-two outpatients with 265 liver lesions were radiologically reviewed; 185 metastases fulfilled the inclusion criteria: 40 DLM, 82 RTLM and 60 SRLM. We observed a pCR rate of 75% (3/4) in resected DLM and 33% (12/36) of local relapse for DLM left in situ. We observed a risk of relapse of 29% and 57% for RTLM and SRLM left in situ, respectively, and a pCR rate of about 40% overall for resected lesions. DLM assessed via hepatobiliary contrast-enhanced and DW-MRI very probably indicates a complete response. The surgical removal of small remnants of liver metastases should always be advocated whenever technically possible.

Summary of adverse events.

Correlation between baseline demographics and percent versus absolute breast density with and without adjustment for BMI.

Effects of Raloxifene and/or Lovaza on Relative Plasma Fatty Acid Concentration.

Effects of Raloxifene and/or Lovaza on Absolute Plasma Fatty Acid Concentration.

Preclinical data indicate that omega-3 fatty acids (n-3FA) potentiate the chemopreventive effect of the antiestrogen (AE) tamoxifen against mammary carcinogenesis. The role of n-3FA in breast cancer prevention in humans is controversial. Preclinical and epidemiologic data suggest that n-3FA may be preferentially protective in obese subjects. To directly test the protective effect of n-3FA against breast cancer, we conducted a 2-year, open-label randomized clinical trial in 266 healthy postmenopausal women (50% normal weight, 30% overweight, 20% obese) with high breast density (BD; ≥25%) detected on their routine screening mammograms. Eligible women were randomized to one of the following five groups (i) no treatment, control; (ii) raloxifene 60 mg; (iii) raloxifene 30 mg; (iv) n-3FA lovaza 4 g; and (v) lovaza 4 g plus raloxifene 30 mg. The 2-year change in BD, a validated biomarker of breast cancer risk, was the primary endpoint of the study. In subset analysis, we tested the prespecified hypothesis that body mass index (BMI) influences the relationship between plasma n-3FA on BD. While none of the interventions affected BD in the intention-to-treat analysis, increase in plasma DHA was associated with a decrease in absolute breast density but only in participants with BMI >29. Our results suggest that obese women may preferentially experience breast cancer risk reduction from n-3FA administration. Cancer Prev Res; 9(4); 275–82. ©2015 AACR.

Supplementary Figure 2 - Patient characteristics in 6 cohorts analysed

Supplementary Figure 3 - Clinical characteristics of EphA2high and EphA2low patients in cohort 1 to 6

Purpose: EphA2 receptor is involved in multiple cross-talks with other cellular networks, including EGFR, FAK, and VEGF pathways, with which it collaborates to stimulate cell migration, invasion, and metastasis. Colorectal cancer (CRC) EphA2 overexpression has also been correlated to stem-like properties of cells and tumor malignancy. We investigated the molecular cross-talk and miRNAs modulation of the EphA2 and EGFR pathways. We also explored the role of EphA2/EGFR pathway mediators as prognostic factors or predictors of cetuximab benefit in patients with CRC.Experimental Design: Gene expression analysis was performed in EphA2high cells isolated from CRC of the AOM/DSS murine model by FACS-assisted procedures. Six independent cohorts of patients were stratified by EphA2 expression to determine the potential prognostic role of a EphA2/EGFR signature and its effect on cetuximab treatment response.Results: We identified a gene expression pattern (EphA2, Efna1, Egfr, Ptpn12, and Atf2) reflecting the activation of EphA2 and EGFR pathways and a coherent dysregulation of mir-26b and mir-200a. Such a pattern showed prognostic significance in patients with stage I–III CRC, in both univariate and multivariate analysis. In patients with stage IV and WT KRAS, EphA2/Efna1/Egfr gene expression status was significantly associated with poor response to cetuximab treatment. Furthermore, EphA2 and EGFR overexpression showed a combined effect relative to cetuximab resistance, independently from KRAS mutation status.Conclusions: These results suggest that EphA2/Efna1/Egfr genes, linked to a possible control by miR-200a and miR-26b, could be proposed as novel CRC prognostic biomarkers. Moreover, EphA2 could be linked to a mechanism of resistance to cetuximab alternative to KRAS mutations. Clin Cancer Res; 23(1); 159–70. ©2016 AACR.

Supplementary Table 3 - Univariate and multivariate analyses of factors affecting PFS in patients who received Cetuximab monotherapy belonging to EphA2high group (cohort 5, N=40).

Kaplan-Meier survival curves of EGFRhigh (dashed line) versus EGFRlow (solid line) for cohort 1, 2 and 3. P-values were calculated using log-rank tests. Tick marks represent censored data. Expression value thresholds for determining high and low groups were found through maxstat R package. For the analysis conducted only for patients belonging to EphA2high group (below figures) Hazard Ratio and 95% Confidence Intervals are reported below each cohort analysed.

Supplementary Table 2A. KRAS mutational status vs. EphA2 expression (N = 70; P = 0.133{section sign}); 2B. Response rate vs. EphA2 expression (N = 68; P = 0.33{section sign}); 2C. Disease control rate vs. EphA2 expression (N = 68; P = 0.012{section sign}); 2D. Response rate vs. EphA2 expression (In KRAS WT patients; N = 39; P = 0.574{section sign}); 2E. Disease control rate vs. EphA2 expression (In KRAS WT patients; N = 39; P = 0.008{section sign})

Supplementary Table 1 - Univariate and multivariate analyses of factors affecting DFS of patients with EphA2high from pooled cohorts 1, 2, and 3 (N = 455).

Kaplan-Meier survival curves of (A) Ptpn12 (high versus low for EphA2high group) (B) Atf2 (high versus low for EphA2high group) and (C) Pik3CG (high versus low for EphA2high group) for cohorts in which results were significant. P-values were calculated using log-rank tests. Expression value thresholds for determining high and low groups were determined through maxstat R package. Tick marks represent censored data.

Supplementary Figure 1 - TaqMan assays ID (Applied Biosystems)

In this note, we study the optimal control of a nonisothermal phase field system of Cahn--Hilliard type that constitutes an extension of the classical Caginalp model for nonisothermal phase transitions with a conserved order parameter. The system couples a Cahn--Hilliard type equation with source term for the order parameter with the universal balance law of internal energy. In place of the standard Fourier form, the constitutive law of the heat flux is assumed in the form given by the theory developed by Green and Naghdi, which accounts for a possible thermal memory of the evolution. This has the consequence that the balance law of internal energy becomes a second-order in time equation for the thermal displacement or freezing index, that is, a primitive with respect to time of the temperature. Another particular feature of our system is the presence of the source term in the equation for the order parameter, which entails additional mathematical difficulties because the mass conservation of the order parameter, typical of the classic Cahn--Hilliard equation, is no longer satisfied. In this paper, we analyze the case that the double-well potential driving the evolution of the phase transition is differentiable, either (in the regular case) on the whole set of reals or (in the singular logarithmic case) on a finite open interval; nondifferentiable cases like the double obstacle potential are excluded from the analysis. We prove the Fréchet differentiability of the control-to-state operator between suitable Banach spaces for both the regular and the logarithmic cases and establish the solvability of the corresponding adjoint systems in order to derive the associated first-order necessary optimality conditions for the optimal control problem. Crucial for the whole analysis to work is the so-called ``strict separation property'', which states that the order parameter attains its values in a compact subset of the interior of the effective domain of the nonlinearity. While this separation property turns out to be generally valid for regular potentials in three dimensions of space, it can be shown for the logarithmic case only in two dimensions.