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Bioaccumulation of dissolved elemental mercury (DGM) by various organisms has been demonstrated, but no study has shown its uptake and sequestration by phytoplankton species. The present study aims to investigate the accumulation of mercury by phytoplankton species exposed to DGM. Diatoms (Cyclotella meneghiniana and Navicula pelliculosa) and green algae (Chlamydomonas reinhardtii and Haematococcus pluvialis) were exposed to constant high level of atmospheric gaseous Hg (∼7.7 µg m−3). Total mercury concentrations (THg) in the medium (dissolved fraction) and algae cells (cellular fraction) were determined using cold vapor atomic fluorescence spectroscopy. Results revealed a partitioning of Hg(0) between the atmosphere and phytoplankton cultures, with THg predominantly found in the algae cells. THg in the algae cultures decreased in the order: C. reinhardtii > H. pluvialis > N. pelliculosa > C. meneghiniana. However, the cellular concentration (mol cell−1) decreased in the order: H. pluvialis > C. reinhardtii > C. meneghiniana > N. pelliculosa. These results highlight species specificity in Hg accumulation upon exposure to DGM, further linked to the phytoplankton surface area. Our findings reveal for the first time that phytoplankton species significantly influence the partitioning of atmospheric Hg(0) in aquatic environments, with important implications for the understanding of the aquatic mercury cycle.

Abstract Clinical depression is characterized by multiple concurrent symptoms, manifesting as a complex heterogeneous condition. Although some well-established classical behavioral assessments are widespread in rodent models, it remains uncertain whether rats also display stress-induced depression-related phenotypes in a multidimensional manner, i.e., simultaneous alterations in multiple behavioral tests. Here, we investigated multivariate patterns and profiles of depression-related behavioral traits in male Wistar rats subjected to inescapable footshocks (IS) or no-shocks (NS), followed by a comprehensive battery of behavioral tests and ethological characterization. We observed generalized stronger intra-test but weaker inter-test correlations. However, feature clustering of behavioral measures successfully delineated variables linked to resilience and susceptibility to stress. Accordingly, a noteworthy covariation pattern emerged, characterized by increased open field locomotion, reduced time in the elevated plus maze open arms, lower sucrose preference, and increased shuttle box escape failures that consistently differentiated IS from NS. Surprisingly there is little contribution from forced swim. In addition, individual clustering revealed a diversity of behavioral profiles, naturally separating NS and IS, including subpopulations entirely characterized by resilience or susceptibility. In conclusion, our study elucidates intricate relationships among classical depression-related behavioral measures, highlighting multidimensional individual variability. Our work emphasizes the importance of a multivariate framework for behavioral assessment in animal models to understand stress-related neuropsychiatric disorders.

Abstract Background Deficits in executive function (EF) are consistently reported in autism spectrum disorders (ASD). Tailored cognitive training tools, such as neurofeedback, focused on executive function enhancement might have a significant impact on the daily life functioning of individuals with ASD. We report the first real-time fMRI neurofeedback (rt-fMRI NF) study targeting the left dorsolateral prefrontal cortex (DLPFC) in ASD. Methods Thirteen individuals with autism without intellectual disability and seventeen neurotypical individuals completed a rt-fMRI working memory NF paradigm, consisting of subvocal backward recitation of self-generated numeric sequences. We performed a region-of-interest analysis of the DLPFC, whole-brain comparisons between groups and, DLPFC-based functional connectivity. Results The ASD and control groups were able to modulate DLPFC activity in 84% and 98% of the runs. Activity in the target region was persistently lower in the ASD group, particularly in runs without neurofeedback. Moreover, the ASD group showed lower activity in premotor/motor areas during pre-neurofeedback run than controls, but not in transfer runs, where it was seemingly balanced by higher connectivity between the DLPFC and the motor cortex. Group comparison in the transfer run also showed significant differences in DLPFC-based connectivity between groups, including higher connectivity with areas integrated into the multidemand network (MDN) and the visual cortex. Conclusions Neurofeedback seems to induce a higher between-group similarity of the whole-brain activity levels (including the target ROI) which might be promoted by changes in connectivity between the DLPFC and both high and low-level areas, including motor, visual and MDN regions.

This article is the authors’ last contribution to a trilogy of research papers submitted to Energies’ Special Issue on Electromagnetic Field Computation, aimed at the theoretical analysis and numerical computation of the frequency-dependent complex impedance of hemispherical electrodes. In this work, we consider a pair of distant identical hemispherical electrodes buried in the ground, whose constitutive parameters (conductivity and permittivity) are assigned diverse values. Simulation experiments carried out using a full-wave finite element method, considering different combinations of the earth’s constitutive parameters, reveal that the grounding impedance of the electrode system can exhibit surprisingly varied frequency behavior. For frequencies close to zero, the impedance can start out inductive or capacitive, then go through a number of resonant transitions between inductive and capacitive states, finally tending towards purely resistive behavior. The results are interpreted using theoretical approximations valid for low- and high-frequency regimes.

The microalgae Chlorella vulgaris and Tetraselmis chui are valued for their nutrient-rich content, including lipids and polyunsaturated fatty acids (PUFA). However, little is known about how storage and processing affect their lipid quality. This study aimed to assess the impact of domestic storage and cooking practices in dried biomass of C. vulgaris and T. chui. Four conditions were tested: control (newly opened package), light (storage at room temperature and daily light regimen for three weeks), frozen (storage in the freezer at −20 °C for three weeks), and heated (three cycles of 90 min at 100 °C). Lipid extracts were analyzed by GC-MS and LC-MS, and antioxidant activity through DPPH and ABTS radical scavenging assays. Tested storage conditions promoted a decrease in fatty acid content and in diacyl/lyso lipid species ratios of phospholipid (PC/LPC, PE/LPE) and betaine lipids (DGTS/MGTS). Lipid extracts from light treatment showed the lowest antioxidant activity in C. vulgaris (ABTS, IC40: 104.9; DPPH, IC20: 187.9 ± 15.0), while heat affected the antioxidant activity of T. chui (ABTS, IC40: 88.5 ± 2.8; DPPH, IC20 209.4 ± 10.9). These findings underscore the impact of managing storage and processing conditions to optimize the nutritional and functional benefits of C. vulgaris and T. chui in food and feed applications.

Abstract Functional near-infrared spectroscopy (fNIRS) provides a cost-efficient and portable alternative to functional magnetic resonance imaging (fMRI) for assessing cortical activity changes based on hemodynamic signals. The spatial and temporal underpinnings of the fMRI blood-oxygen-level-dependent (BOLD) signal and corresponding fNIRS concentration of oxygenated (HbO), deoxygenated (HbR), and total hemoglobin (HbT) measurements are still not completely clear. We aim to analyze the spatial correspondence between these hemodynamic signals, in motor-network regions. To this end, we acquired asynchronous fMRI and fNIRS recordings from 9 healthy participants while performing motor imagery and execution. Using this multimodal approach, we investigated the ability to identify motor-related activation clusters in fMRI data using subject-specific fNIRS-based cortical signals as predictors of interest. Group-level activation was found in fMRI data modeled from corresponding fNIRS measurements, with significant peak activation found overlapping the individually-defined primary and premotor motor cortices, for all chromophores. No statistically significant differences were observed in multimodal spatial correspondence between HbO, HbR, and HbT, for both tasks. This suggests the possibility of translating neuronal information from fMRI into an fNIRS motor-coverage setup with high spatial correspondence using both oxy and deoxyhemoglobin data, with the inherent benefits of translating fMRI paradigms to fNIRS in cognitive and clinical neuroscience.

Introduction: Over 90% of the patients with familial adenomatous polyposis (FAP) will develop duodenal adenomas. Aim: The aim of this study was to evaluate the effectiveness and safety of endoscopic excision of large duodenal adenomas in FAP patients. Methods: All FAP patients from a familial risk clinic submitted to endoscopic therapy for duodenal adenomas ≥10 mm between January 2010 and February 2021 were included. Results: From 151 FAP families, 22 patients (50 lesions) were included: 54.5% female; median follow-up 8.5 (IQR: 5.8–12.3) years after the first endoscopy. First therapeutic endoscopy occurred at a median age of 41.0 years (IQR: 33.0–58.2). Repeat therapeutic endoscopy was required in 54.5% of patients. Median size of the largest adenoma was 15 mm (IQR: 10–18 mm); resection was piecemeal in 63.1% and en bloc in the remaining. In 2 cases, the resection was incomplete (fibrosis due to previous resection and difficult positioning). Complications occurred in 6.3% of the resected lesions (4 patients): 2 immediate (bleeding, perforation); 4 in the first week (1 bleeding, 2 mild pancreatitis, 1 perforation requiring surgery; the latter two after ampullectomy). Histology revealed low-grade dysplasia adenomas in 90.1%; no adenocarcinomas were found. One patient with Spigelman stage IV disease not amenable to endoscopic control underwent elective duodenopancreatectomy (without duodenal cancer). Conclusion: Endoscopic surveillance and treatment of duodenal adenomas in FAP patients was safe and effective in the prevention of duodenal cancer.

To ensure the acceptable mechanical strength of amorphous wollastonitic hydraulic binders (AWHs), activation with a sodium silicate solution is necessary. However, the use of this type of activator increases the final cost and the complexity of the product’s overall use. In this work, we focus on enhancing the manufacturing of the alkaline activator by producing three Na2SiO3 powders using cost-effective raw materials. The procedure consisted of heating a mixture of NaOH pebbles with either sand, glass, or diatomite to a temperature of 330 °C for 2 h. After synthesis, the powders were characterized by Fourier Transform Infrared Spectroscopy (FTIR) and X-ray Diffraction (XRD) techniques. Finally, mortars made with AWHs were activated using the synthesized powders that were added either as a solid or dissolved in an aqueous solution. The compressive strength results in these mortars show that the lab-made activators are competitive with the traditional sodium silicate activators. Furthermore, the synthetized activators can be added in either solid form or pre-dissolved in a solution. This innovative approach represents a more economical, sustainable and easy-to-use approach to enhancing the competitiveness of AWHs.

Metallic electrodes are widely used in many applications, the analysis of their frequency-domain behavior is an important subject, particularly in applications related to earthing/grounding systems, from dc up into the MHz range. In this paper, a numerical evaluation of the frequency-dependent complex impedance of the hemispherical ground electrode is implemented. A closed-form solution for non-zero frequencies is still a difficult task to achieve as evidenced in a previous paper dedicated to the subject and, therefore, numerical approaches should be an alternative option. The aim of this article is to present a solution based on a numerical method using finite element analysis. In typical commercial FE tools, electric currents exhibit azimuthal orientation and, as such, the magnetic field has a null azimuthal component but non-null axial and radial components. On the contrary, a dual problem is considered in this work, with a purely azimuthal magnetic field. To overcome the difficulty of directly using a commercial FE tool, a novel formulation is developed. An innovative 2D formulation, the ι-form, is developed as a modification of the H-formulation applied to axisymmetric magnetic field problems. The results are validated using a classical 3D H-formulation; comparisons showed very good agreement. The electrode complex impedance is analyzed considering two different cases. Firstly, the grounding system is constituted by a hemispherical electrode surrounded by a remote concentric electrode; in the second case, the grounding system is constituted by two identical thin hemispherical electrodes. Computed results are presented and discussed, showing how the grounding impedance depends on the frequency and, also, on the radius of the remote concentric electrode (first case) or on the distance between the two hemispherical electrodes (second case).

This paper explores the opportunities and challenges for classifying human posture in indoor scenarios by analyzing the Frequency-Modulated (FM) radio broadcasting signal received at multiple locations. More specifically, we present a passive RF testbed operating in FM radio bands, which allows experimentation with innovative human posture classification techniques. After introducing the details of the proposed testbed, we describe a simple methodology to detect and classify human posture. The methodology includes a detailed study of feature engineering and the assumption of three traditional classification techniques. The implementation of the proposed methodology in software-defined radio devices allows an evaluation of the testbed’s capability to classify human posture in real time. The evaluation results presented in this paper confirm that the accuracy of the classification can be approximately 90%, showing the effectiveness of the proposed testbed and its potential to support the development of future innovative classification techniques by only sensing FM bands in a passive mode.

Everyday tasks use sensors to monitor and provide information about processes in different scenarios, such as monitoring devices in manufacturing or homes. Sensors need to communicate, with or without wires, while providing secure information. Power can be derived from various energy sources, such as batteries, electrical power grids, and energy harvesting. Energy harvesting is a promising way to provide a sustainable and renewable source to power sensors by scavenging and converting energy from ambient energy sources. However, low energy is harvested through these methods. Therefore, it is becoming a challenge to design and deploy wireless sensor networks while ensuring the sensors have enough power to perform their tasks and communicate with each other through careful management and optimization, matching energy supply with demand. For this reason, data cryptography and authentication are needed to protect sensor communication. This paper studies how energy harvested with microbial fuel cells can be employed in algorithms used in data protection during sensor communication.

Executive functions and motivation have been established as key aspects for neurofeedback success. However, task-specific influence of cognitive strategies is scarcely explored. In this study, we test the ability to modulate the dorsolateral prefrontal cortex, a strong candidate for clinical application of neurofeedback in several disorders with dysexecutive syndrome, and investigate how feedback contributes to better performance in a single session. Participants of both neurofeedback (n = 17) and sham-control (n = 10) groups were able to modulate DLPFC in most runs (with or without feedback) while performing a working memory imagery task. However, activity in the target area was higher and more sustained in the active group when receiving feedback. Furthermore, we found increased activity in the nucleus accumbens in the active group, compared with a predominantly negative response along the block in participants receiving sham feedback. Moreover, they acknowledged the non-contingency between imagery and feedback, reflecting the impact on motivation. This study reinforces DLPFC as a robust target for neurofeedback clinical implementations and enhances the critical influence of the ventral striatum, both poised to achieve success in the self-regulation of brain activity.

BackgroundLittle is known about patient preferences and the value of pharmacy-collaborative disease management with primary care using technology-driven interprofessional communication under real-world conditions. Discrete Choice Experiments (DCEs) are useful for quantifying preferences for non-market services.Objectives1) To explore variation in patient preferences and estimate willingness-to-accept annual cost to the National Health Service (NHS) for attributes of a collaborative intervention trial between pharmacies and primary care using a trial exit DCE interview; 2) to incorporate a DCE into an economic evaluation using cost-benefit analysis (CBA).MethodsWe performed a DCE telephone interview with a sample of hypertension and hyperlipidemia trial patients 12 months after trial onset. We used five attributes (levels): waiting time to get urgent/not urgent medical appointment (7 days/45 days; 48 hrs./30 days; same day/15 days), model of pharmacy intervention (5-min. counter basic check; 15-min. office every 3 months for BP and medication review of selected medicines; 30-min. office every 6 months for comprehensive measurements and medication review of all medicines), integration with primary care (weak; partial; full), chance of having a stroke in 5 years (same; slightly lower; much lower), and annual cost to the NHS (0€; 30€; 51€; 76€). We used an experimental orthogonal fractional factorial design. Data were analyzed using conditional logit. We subtracted the estimated annual incremental trial costs from the mean WTA (Net Benefit) for CBA.ResultsA total of 122 patients completed the survey. Waiting time to get medical appointment-on the same day (urgent) and within 15 days (non-urgent)-was the most important attribute, followed by 30-minute pharmacy intervention in private office every 6 months for point-of-care measurements and medication review of all medicines, and full integration with primary care. The cost attribute was not significant. Intervention patients were willing to accept the NHS annual cost of €877 for their preferred scenario. The annual net benefit per patient is €788.20 and represents the monetary value of patients' welfare surplus for this model.ConclusionsThis study is the first conducted in Portugal alongside a pharmacy collaborative trial, incorporating DCE into CBA. The findings can be used to guide the design of pharmacy collaborative interventions with primary care with the potential for reimbursement for uncontrolled or at-risk chronic disease patients informed by patient preferences. Future DCE studies conducted in community pharmacy may provide additional contributions.Trial registrationCurrent Controlled Trials (ISRCTN): ISRCTN13410498, retrospectively registered on 12 December 2018.

Functional magnetic resonance imaging (fMRI) has been extensively used as a tool to map the brain processes related to somatosensory stimulation. This mapping includes the localization of task-related brain activation and the characterization of brain activity dynamics and neural circuitries related to the processing of somatosensory information. However, the magnetic resonance (MR) environment presents unique challenges regarding participant and equipment safety and compatibility. This study aims to systematically review and analyze the state-of-the-art methodologies to assess the safety and compatibility of somatosensory stimulation devices in the MR environment. A literature search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines, was performed in PubMed, Scopus, and Web of Science to find original research on the development and testing of devices for somatosensory stimulation in the MR environment. Nineteen records that complied with the inclusion and eligibility criteria were considered. The findings are discussed in the context of the existing international standards available for the safety and compatibility assessment of devices intended to be used in the MR environment. In sum, the results provided evidence for a lack of uniformity in the applied testing methodologies, as well as an in-depth presentation of the testing methodologies and results. Lastly, we suggest an assessment methodology (safety, compatibility, performance, and user acceptability) that can be applied to devices intended to be used in the MR environment.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021257838.

Resumo Objetivo Avaliar o emplastro de lidocaína 5% como método de tratamento da dor neuropática após cirurgias ortopédicas em comparação com massagem terapêutica realizada sobre incisões. Métodos Trata-se de um ensaio clínico prospectivo, randomizado, com 37 pacientes submetidos a cirurgia ortopédica entre janeiro de 2015 e fevereiro de 2017. Foram incluídos pacientes com idade entre 13 e 70 anos que foram submetidos a cirurgia ortopédica no pé e tornozelo com dor neuropática ou hipersensibilidade na incisão cirúrgica por no mínimo 90 dias após o procedimento. Todos os indivíduos foram avaliados segundo a escala visual analógica (EVA) de dor e o questionário de qualidade de vida SF-36 no início do tratamento e após 30, 60 e 90 dias. Resultados Os dois grupos apresentaram melhora da dor; porém, o grupo que utilizou o emplastro apresentou maior redução com o passar do tempo. Em relação aos parâmetros do questionário SF-36, nenhum deles demonstrou diferença estatisticamente relevante. Em relação à capacidade funcional, aos aspectos físicos, à vitalidade, aos aspectos emocionais, aos aspectos sociais, ao estado geral de saúde e saúde mental, não houve evidências significativas. A grande vantagem do emplastro está no grau de satisfação pessoal dos pacientes, com relevância estatística, provavelmente pela facilidade de aplicação e pelo efeito psicológico de uma terapia medicamentosa. Conclusão O emplastro e a massagem são métodos de tratamento eficazes na redução da dor cicatricial, apresentando resultados semelhantes. O emplastro está associado à melhora do grau de satisfação dos pacientes. Nível de Evidência 1. Ensaio clínico prospectivo randomizado.

The accumulation of protons in electro-active biofilms (EABfs) has been reported as a critical parameter determining produced currents at the anode since the very beginning of the studies on Bio-electrochemical systems (BESs). Even though the knowledge gained on the influence of this parameter on the produced currents, its influence on EABfs growth is frequently overlooked. In this study, we quantified EABfs thicknesses in real-time and related them to the produced current at three buffer concentrations, two anode potentials and two acetate concentrations. The thickest EABfs (80 μm) and higher produced currents (2.5 A.m−2) were measured when a 50 mM buffer concentration was used. By combining the measured EABfs thicknesses with the pH in the anolyte, a simple model was developed to identify buffer limitations. Buffer limited EABfs with thicknesses of 15 and 42 μm were identified at −0.3 V vs Ag/AgCl when 10 and 50 mM buffer concentrations were used, respectively. At −0.2 V vs Ag/AgCl, the thicknesses of buffer limited EABfs decreased to 13 and 20 μm, respectively. The model also estimated buffer and acetate diffusion rates in EABfs and allowed to determine the boundary between a buffer and acetate limited EABfs. The diffusion rates reported in this study and the definition of the boundary between buffer and acetate limited EABfs provide a powerful tool to avoid limitations, leading to higher produced currents at the anode.

Electro-active bacteria (EAB) can form biofilms on an anode (so-called bioanodes), and use the electrode as electron acceptor for oxidation of organics in wastewater. So far, bioanodes have mainly been investigated under a continuous anode potential, but intermittent anode potential has resulted in higher currents and different biofilm morphologies. However, little is known about how intermittent potential influences the electron balance in the anode compartment. In this study, we investigated electron balances of bioanodes at intermittent anode potential regimes. We used a transparent non-capacitive electrode that also allowed for in-situ quantification of the EAB using optical coherence tomography (OCT). We observed comparable current densities between continuous and intermittent bioanodes, and stored charge was similar for all the applied intermittent times (5 mC). Electron balances were further investigated by quantifying Extracellular Polymeric Substances (EPS), by analyzing the elemental composition of biomass, and by quantifying biofilm and planktonic cells. For all tested conditions, a charge balance of the anode compartment showed that more electrons were diverted to planktonic cells than biofilm. Besides, 27–43% of the total charge was detected as soluble EPS in intermittent bioanodes, whereas only 15% was found as soluble EPS in continuous bioanodes. The amount of proteins in the EPS of biofilms was higher for intermittent operated bioanodes (0.21 mg COD proteins mg COD biofilm−1) than for continuous operated bioanodes (0.05 mg COD proteins mg COD biofilm−1). OCT revealed patchy morphologies for biofilms under intermittent anode potential. Overall, this study helped understanding that the use of a non-capacitive electrode and intermittent anode potential deviated electrons to other processes other than electric current at the electrode by identifying electron sinks in the anolyte and quantifying the accumulation of electrons in the form of EPS.

Objective:This study aimed to analyze the outcomes of patients with recurrent prostate cancer (PCa) who received salvage cryotherapy (SC) in our institution. Biochemical recurrence (BCR) after definitive radiotherapy or brachytherapy for PCa is usually managed with long-term androgen-deprivation therapy (ADT). In selected cases, salvage therapies might delay ADT and its side effects.Materials and Methods:All patients who received SC from 2014 to 2018 in our institution were evaluated retrospectively.Results:A total of 17 patients were included, with a median age at SC of 72.0 (range 60-77) years. The median prostate-specific antigen (PSA) before SC was 4.25 [interquartile range (IQR) 3.1-7.6] ng/mL. The median time to BCR was 18.8 (IQR 13.5-32.1) months after SC. The median PSA nadir after SC was 0.49 (IQR 0.09-1.0) ng/mL. With a median follow-up of 43 (range, 11-78) months, 7 (41%) patients had a recurrence. Of those patients, two received ADT, while others were managed conservatively. The biochemical progression-free survival (bPFS) time of patients with PSA nadir 8 ng/mL were also associated with shorter bPFS (log-rank test, p

Background: There is little experience in the economic evaluation of pharmacy/primary care collaborative health interventions using interprofessional technology-driven communication under real-world conditions. This study aimed to conduct cost-effectiveness and cost-utility analyses of a collaborative care intervention in hypertension and hyperlipidemia management between pharmacies and primary care versus usual (fragmented) care alongside a trial.Methods: An economic evaluation was conducted alongside a 6-month pragmatic quasi-experimental controlled trial. Data sources included primary care clinical software; pharmacy dispensing software; patient telephone surveys; and published literature. The target population was adult patients on hypertension and/or lipid-lowering medication. The perspective was societal. We collected patient-level data on resource use to estimate trial costs. Effect outcomes included blood pressure (BP) and quality-adjusted life years (QALYs). Bootstrapping was used to estimate uncertainty around the incremental cost-effectiveness and cost-utility ratios. Cost-effectiveness planes and acceptability curves were estimated.Results: The intervention was not shown to have reasonable levels of cost-effectiveness or cost-utility when compared to usual care as denoted by the levels of uncertainty expressed in wide confidence intervals. The probability of the intervention being cost-effective is 28% at the threshold of €20,000 per QALY gained and 57% at the threshold of €500 per mmHg systolic BP decrease.Conclusion: Considering the limitations of the trial which affected effectiveness and economic outcomes, our results are not generalizable for community pharmacy and primary care in Portugal. This research offers, however, valuable lessons on methods and strategies that can be used in future economic evaluations of collaborative public health interventions with the potential for reimbursement.Clinical trial registration:https://www.isrctn.com/ISRCTN13410498, identifier ISRCTN13410498

Introduction: Health technology assessment (HTA) aims to provide decision makers with relevant data to make informed choices. Recent changes in the Portuguese HTA framework have altered substantially the assessment methodology with regard to economic evaluation, with potential impacts on access and process efficiency. The HTA Reshaping Project had as its main objective informing the debate on HTA in Portugal, thereby identifying improvement opportunities and solutions to the HTA framework that address future challenges. Methods: The project comprised several phases, i.e., (1) mapping and evaluation of different HTA frameworks across Europe, identifying best practices and key variables to consider in future frameworks; (2) conduction of in-depth interviews with relevant stakeholders (n = 11); and (3) development of 2 workshops – one with young professionals (n = 12) and another with relevant HTA stakeholders (n = 19) – to consolidate and further explore vital elements of HTA, aimed at brainstorming ideas and developing solutions to improve some of the most critical points, with a view to addressing future challenges. Results: The comparison of HTA frameworks showed that their purpose and sophistication vary across European countries. For example, the need for economic evidence is not unanimous, and reimbursement agreements vary considerably. Among the stakeholders interviewed there was a high level of agreement on priorities that should be addressed, e.g., expanding and creating national level registries and assuring patient participation throughout the HTA process. The possibility of using managed entry agreements to enhance patients’ access, applying multi-indication pricing for medicines with different therapeutic values per indication, and improvement of registry/system interoperability gathered a moderate level of agreement. Conclusions: The Portuguese HTA framework might be further adapted to upcoming challenges and should evolve to improve access to innovative therapies. There is still a long path towards the convergence of HTA frameworks in EU member states.

Obesity surgery candidates are at an increased risk of kidney injury, but pre-operative evaluation usually neglects kidney function assessment. This study aimed to identify renal dysfunction in candidates for bariatric surgery. To reduce the sources of bias, subjects with diabetes, prediabetes under metformin treatment, neoplastic or inflammatory diseases were excluded. Patients’ (n = 192) average body mass index was 41.7 ± 5.4 kg/m2. Among these, 51% (n = 94) had creatinine clearance over 140 mL/min, 22.4% (n = 43) had proteinuria over 150 mg/day and 14.6% (n = 28) albuminuria over 30 mg/day. A creatinine clearance higher than 140 mL/min was associated with higher levels of proteinuria and albuminuria. Univariate analysis identified sex, glycated hemoglobin, uric acid, HDL and VLDL cholesterol as being associated with albuminuria, but not with proteinuria. On multivariate analysis, glycated hemoglobin and creatinine clearance as continuous variables were significantly associated with albuminuria. In summary, in our patient population prediabetes, lipid abnormalities and hyperuricemia were associated with albuminuria, but not with proteinuria, suggesting different disease mechanisms might be implicated. Data suggest that in obesity-associated kidney disease, tubulointerstitial injury precedes glomerulopathy. A significant proportion of obesity surgery candidates present clinically relevant albuminuria and proteinuria along with renal hyperfiltration, suggesting that routine pre-operative assessment of these parameters should be considered.

Abstract Background In current guidelines, endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is recommended in pancreatic cystic lesions (PCLs) with worrisome features (size ≥ 3 cm, mural nodule, or Wirsung dilation). Objective To evaluate the diagnostic ability and assess the accuracy of EUS-FNA in PCLs smaller than 3 cm. Methods Retrospective study of PCLs

The use of transcranial Electrical Stimulation (tES) in the modulation of cognitive brain functions to improve neuropsychiatric conditions has extensively increased over the decades. tES techniques have also raised new challenges associated with study design, stimulation protocol, functional specificity, and dose-response relationship. In this paper, we addressed challenges through the emerging methodology to investigate the dose-response relationship of High Definition-transcranial Direct Current Stimulation (HD tDCS), identifying the role of negative valence in tinnitus perception. In light of the neurofunctional testable framework and tES application, hypotheses were formulated to measure clinical and surrogate endpoints. We posited that conscious pairing adequately pleasant stimuli with tinnitus perception results in correction of the loudness misperception and would be reinforced by concurrent active HD-tDCS on the left Dorsolateral Prefrontal Cortex (dlPFC). The dose-response relationship between HD-tDCS specificity and the loudness perception is also modeled. We conducted a double-blind, randomized crossover pilot study with six recruited tinnitus patients. Accrued data was utilized to design a well-controlled adaptive seamless Bayesian dose-response study. The sample size (n = 47, for 90% power and 95% confidence) and optimum interims were anticipated for adaptive decision-making about efficacy, safety, and single session dose parameters. Furthermore, preliminary pilot study results were sufficient to show a significant difference (90% power, 99% confidence) within the longitudinally detected self-report tinnitus loudness between before and under positive emotion induction. This study demonstrated a research methodology used to improve emotion regulation in tinnitus patients. In the projected method, positive emotion induction is essential for promoting functional targeting under HD-tDCS anatomical specificity to indicate the efficacy and facilitate the dose-finding process. The continuous updating of prior knowledge about efficacy and dose during the exploratory stage adapts the anticipated dose-response model. Consequently, the effective dose range to make superiority neuromodulation in correcting loudness misperception of tinnitus will be redefined. Highly effective dose adapts the study to a standard randomized trial and transforms it into the confirmatory stage in which active HD-tDCS protocol is compared with a sham trial (placebo-like). Establishing the HD-tDCS intervention protocols relying on this novel method provides reliable evidence for regulatory agencies to approve or reject the efficacy and safety. Furthermore, this paper supports a technical report for designing multimodality data-driven complementary investigations in emotion regulation, including EEG-driven neuro markers, Stroop-driven attention biases, and neuroimaging-driven brain network dynamics.

Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy and is frequently drug-resistant (DR) to antiseizure medication (ASM), corresponding to approximately one-third of the cases. When left inadequately treated, it can worsen the quality of life, cognitive deficits, and risk of death. The standard treatment for drug-resistant TLE is the surgical removal of the structures involved, with good long-term outcome rates of 60–70 % and a low rate of adverse effects. The goal of successful treatment is sustained seizure freedom. In our study, we evaluated sustained long-term (up to 23 years) surgical outcomes in 621 patients with DR-TLE associated with hippocampal sclerosis, who underwent a temporal lobectomy. We analyzed the main predictive factors that influence the surgical outcome related to seizure control, through a longitudinal and retrospective study, using a multivariable regression model. We found that 73.6% of the patients were free from disabling seizures (Engel Class I), maintained over time in 65% of patients followed up to 23 years after surgery. We found that four independent variables predicted seizure outcomes. The presence of dysmnesic and olfactory aura predicted a less favorable outcome. The history of febrile seizure and the surgical technique predicted a good outcome. Regarding the type of surgical technique, the standard anteromesial temporal lobectomy (ATL) led to significantly better outcomes (78.6% Engel Class I) when compared to the selective amygdalohippocampectomy via subtemporal approach (67.2% Engel Class I; p = 0.002), suggesting that the neuronal networks involved in the epileptogenic zone may be beyond mesial temporal structures. The multivariable regression model with the above-mentioned predictor variables revealed an ExpB = 3.627 (N = 621, p < 0.001), indicating that the model was able to distinguish between patients with a seizure-free. We conclude that epilepsy surgery is a safe procedure, with low rates of postoperative complications and good long-term results.

Introduction: Patients with colonic inflammatory bowel disease (IBD) are at an increased risk for colorectal cancer (CRC), whereby surveillance colonoscopy is recommended. Aim: To study the clinical and endoscopic variables associated with dysplasia in IBD patients. Methods: A cohort study was conducted on IBD patients who were part of a colonoscopy surveillance program between 2011 and 2016. Results: A total of 342 colonoscopies were performed on 162 patients (105 with ulcerative colitis [UC] and 57 with Crohn’s disease). Random biopsies were performed at least once on 81.5% of patients; 33.3% of the patients underwent chromoendoscopy (CE) at least once. Endoscopically resectable lesions were detected in 55 patients (34%), and visible lesions deemed unfit for endoscopic resection were found in 5 patients (3.1%). Overall, 62 dysplastic visible lesions (58 with low-grade dysplasia and 3 with high-grade dysplasia) and 1 adenocarcinoma were found in 34 patients. Dysplasia in random biopsies was present in 3 patients, the yield of random biopsies for dysplasia being 1.85%/patient (3/162), 1.75%/colonoscopy (6/342), and 0.25%/biopsy (9/3,637). Dysplasia detected in random biopsies was significantly associated with a personal history of visible dysplasia (p = 0.006). Upon univariate analysis, dysplasia was significantly associated with the type of IBD, the performance of random biopsies, and CE (p = 0.016/0.009/0.05, respectively). On multivariate analysis, dysplasia was associated with duration of disease. Conclusion: Our data confirm that patients with long-standing IBD, in particular UC, should be enrolled in dysplasia surveillance programs, and that performing CE and random biopsies seems to help in the detection of colonic neoplastic lesions.

Resumo Para a elaboração de sua crítica da questão teleológica Nietzsche parte de uma leitura particular das filosofias de Kant, Albert Lange e Schopenhauer. Mais especificamente, sua argumentação em torno da concepção teleológica de mundo, que se constitui em um tema de importância significativa para o posterior desenvolvimento de sua concepção de conhecimento, é fundamentada em uma releitura das posições de Kant e Schopenhauer a partir de uma fundamentação científica. Este posicionamento mais próximo da ciência, uma conquista oriunda da leitura de A História do Materialismo, atua como contraponto às opiniões filosóficas com que Nietzsche entra em contato em sua juventude.

Abstract Introduction The presence of microembolic signals (MES) during the acute phase of stroke is poorly understood, and its role and clinical application in relation to risk stratification and prognosis in patients remain uncertain. We assessed the prevalence of spontaneous MES in acute stroke and their relationship with risk stratification, stroke recurrence, morbidity, and mortality. Patients and methods This was a prospective cohort study conducted in the Stroke Unit. The MES presence was evaluated by transcranial Doppler (TCD) in patients with ischemic stroke within 48 h. The outcomes (risk stratification, morbidity, mortality, and recurrence of a stroke) were followed up for 6 months. The relationship between risk stratification and MES was obtained by odds ratios and that between MES and stroke recurrence, morbidity, and mortality using multiple logistic regression; considering statistical significance at P

Parvalbumin is a calcium-binding protein present in inhibitory interneurons that play an essential role in regulating many physiological processes, such as intracellular signaling and synaptic transmission. Changes in parvalbumin expression are deeply related to epilepsy, which is considered one of the most disabling neuropathologies. Epilepsy is a complex multi-factor group of disorders characterized by periods of hypersynchronous activity and hyperexcitability within brain networks. In this scenario, inhibitory neurotransmission dysfunction in modulating excitatory transmission related to the loss of subsets of parvalbumin-expressing inhibitory interneuron may have a prominent role in disrupted excitability. Some studies also reported that parvalbumin-positive interneurons altered function might contribute to psychiatric comorbidities associated with epilepsy, such as depression, anxiety, and psychosis. Understanding the epileptogenic process and comorbidities associated with epilepsy have significantly advanced through preclinical and clinical investigation. In this review, evidence from parvalbumin altered function in epilepsy and associated psychiatric comorbidities were explored with a translational perspective. Some advances in potential therapeutic interventions are highlighted, from current antiepileptic and neuroprotective drugs to cutting edge modulation of parvalbumin subpopulations using optogenetics, designer receptors exclusively activated by designer drugs (DREADD) techniques, transcranial magnetic stimulation, genome engineering, and cell grafting. Creating new perspectives on mechanisms and therapeutic strategies is valuable for understanding the pathophysiology of epilepsy and its psychiatric comorbidities and improving efficiency in clinical intervention.

ABSTRACT Background: Few Brazilian studies investigated risk factors for dysphagia and associated complications in a large cohort. Objective: To investigate frequency, predictors, and associated outcomes of dysphagia in patients up to three months post-stroke. Methods: Prospective cohort study of consecutively admitted patients in a specialized center for acute stroke. Patients with a transient ischemic attack, subarachnoid hemorrhage, cerebral venous thrombosis, hemorrhagic stroke with secondary cause, non-acute stroke, or those who did not consent to participate were excluded. Swallowing was evaluated by speech language pathologists using Volume-Viscosity Swallow Test. General function at three months post-stroke was assessed using the following instruments: Modified Rankin scale, Barthel Index and Functional Independence Measure. Results: A total of 831 patients were admitted and 305 patients were included according to the inclusion and exclusion criteria. The mean age of patients was 63.6±13.3 years, mean time from stroke to swallowing assessment was 4.2±4.1 days, and 45.2% of the patients had dysphagia. Age (OR=1.02; 95%CI 1.00-1.04; p=0.017), known medical history of obstructive sleep apnea (OR=5.13; 95%CI 1.74-15.15; p=0.003), and stroke severity at hospital admission (OR=1.10; 95%CI 1.06-1.15; p

Genetic predisposition accounts for nearly 10% of all melanoma cases and has been associated with a dozen moderate- to high-penetrance genes, including CDKN2A, CDK4, POT1 and BAP1. However, in most melanoma-prone families, the genetic etiology of cancer predisposition remains undetermined. The goal of this study was to identify rare genomic variants associated with cutaneous melanoma susceptibility in melanoma-prone families. Whole-exome sequencing was performed in 2 affected individuals of 5 melanoma-prone families negative for mutations in CDKN2A and CDK4, the major cutaneous melanoma risk genes. A total of 288 rare coding variants shared by the affected relatives of each family were identified, including 7 loss-of-function variants. By performing in silico analyses of gene function, biological pathways, and variant pathogenicity prediction, we underscored the putative role of several genes for melanoma risk, including previously described genes such as MYO7A and WRN, as well as new putative candidates, such as SERPINB4, HRNR, and NOP10. In conclusion, our data revealed rare germline variants in melanoma-prone families contributing with a novel set of potential candidate genes to be further investigated in future studies.

Background: Sentinel Lymph Node (SLN) status has been shown to be the strongest independent prognostic factor of cutaneous melanoma (CM) stage I-II patients. Few papers on CM at private clinics (PC) are available. Objective: To present clinical and histologic data, complications and frequency of SLN involvement in CM patients diagnosed and followed at a dermatology/cutaneous oncology PC in São Paulo/Brazil, who were submitted to SLNB. Methods: Retrospective, single-center cohort of patients who attended PC from June 1998 to Jan 2020. Electronic files were selected and analyzed. Minimum period for considering the patient eligible was 1 year. Results: 215 CM lesions were identified in 184 patients(1.2 melanoma/patient). Forty-seven patients (25.5%) were submitted to SLNB and 59 SLN for histologic examination (1.2 SLN/patient). 10,9% tested positive. SLN identification happened in 95.7%. In 38/47 (80,8%) patients single LBD was found, while multiple-LBD was found in 9/47(19.1%). Eighteen(72,0%) out of 25 trunk lesions drained to single basin, while in 7 patients multiple LBD was found. Complication rate was 6,0%. Conclusions: Percentage of CM patients that undergo SLNB, node positivity for metastasis, draining basins and complications in this study were similar to studies in northern hemisphere patients. Clinical and epidemiologic characteristics of CM patients differ markedly between PC and PHS patients.

The hippocampus-prefrontal cortex (HPC-PFC) pathway plays a fundamental role in executive and emotional functions. Neurophysiological studies have begun to unveil the dynamics of HPC-PFC interaction in both immediate demands and long-term adaptations. Disruptions in HPC-PFC functional connectivity can contribute to neuropsychiatric symptoms observed in mental illnesses and neurological conditions, such as schizophrenia, depression, anxiety disorders, and Alzheimer’s disease. Given the role in functional and dysfunctional physiology, it is crucial to understand the mechanisms that modulate the dynamics of HPC-PFC communication. Two of the main mechanisms that regulate HPC-PFC interactions are synaptic plasticity and modulatory neurotransmission. Synaptic plasticity can be investigated inducing long-term potentiation or long-term depression, while spontaneous functional connectivity can be inferred by statistical dependencies between the local field potentials of both regions. In turn, several neurotransmitters, such as acetylcholine, dopamine, serotonin, noradrenaline, and endocannabinoids, can regulate the fine-tuning of HPC-PFC connectivity. Despite experimental evidence, the effects of neuromodulation on HPC-PFC neuronal dynamics from cellular to behavioral levels are not fully understood. The current literature lacks a review that focuses on the main neurotransmitter interactions with HPC-PFC activity. Here we reviewed studies showing the effects of the main neurotransmitter systems in long- and short-term HPC-PFC synaptic plasticity. We also looked for the neuromodulatory effects on HPC-PFC oscillatory coordination. Finally, we review the implications of HPC-PFC disruption in synaptic plasticity and functional connectivity on cognition and neuropsychiatric disorders. The comprehensive overview of these impairments could help better understand the role of neuromodulation in HPC-PFC communication and generate insights into the etiology and physiopathology of clinical conditions.

Lightweight structural materials are increasingly sought after in the automotive and aerospace industries for their potential to improve fuel efficiency. Magnesium-based metal-matrix composites are potential candidates for these kinds of applications. The use of recycled carbon fibres offers further energy and cost savings. The recycled carbon fibre composites were manufactured by stir casting with high-dispersion shearing, then were extruded and subsequently heat treated. The compressive deformation mechanisms of the composites compared to AZ91 were investigated using in situ synchrotron radiation diffraction. An increase in ultimate compressive strength was achieved in the composites compared to AZ91. The deformation mechanisms active in the composites were similar to those in AZ91. Magnesium alloys in compression typically show extensive twinning; this was observed in AZ91 and the AZ91 composites. The stress required for twinning onset was increased in the composites, and the twin volume fraction at failure was decreased compared to AZ91.

The shop floor or factory floor is the area inside a factory where manufacturing production is executed. The digitalisation of this area has been increasing in the last few years, introducing the Digital Twin (DT) and the Industry 4.0 concepts. A DT is the digital representation of a real object or an entire system. A DT includes a high diversity of components from different vendors that need to interact with each other efficiently. In most cases, the development of standards and protocols does not consider the need to operate with other standards and protocols, causing interoperability issues. Transducers (sensors and actuators) use the communication layer to exchange information with digital contra parts, and for this reason, the communication layer is one of the most relevant aspects of development. This paper covers DT development, going from the physical to the visualisation layer. The reference architecture models, standards, and protocols focus on interoperability to reach a syntactic level of communication between the IEEE 1451 and the IEC 61499 standards. A semantic communication layer connects transducer devices to the digital representation, achieving a semantic level of interoperability. This communication layer adds semantics to the communication process, allowing the development of an interoperable DT based on the IEEE 1451 standards. The DT presented reaches the syntactic and semantic levels of interoperability, allowing the monitoring and visualisation of a prototype system.

Insomnia is a widespread neuropsychological sleep-related disorder known to result in various predicaments including cognitive impairments, emotional distress, negative thoughts, and perceived sleep insufficiency besides affecting the incidence and aggravation of other medical disorders. Despite the available insomnia-related theoretical cognitive models, clinical studies, and related guidelines, an evidence-based conceptual framework for a personalized approach to insomnia seems to be lacking. This study proposes a conceptual cognitive framework (CCF) providing insight into cognitive mechanisms involved in the predisposition, precipitation, and perpetuation of insomnia and consequent cognitive deficits. The current CCF for insomnia relies on evaluative conditional learning and appraisal which generates negative valence (emotional value) and arousal (cognitive value). Even with the limitations of this study, the suggested methodology is well-defined, reproducible, and accessible can help foster future high-quality clinical databases. During clinical insomnia but not the neutral one, negative mood (trait-anxiety) causes cognitive impairments only if mediating with a distorted perception of insomnia (Ind-1 = 0.161, 95% CI 0.040–0.311). Further real-life testing of the CCF is intended to formulate a meticulous, decision-supporting platform for clinical interventions. Furthermore, the suggested methodology is expected to offer a reliable platform for CCF-development in other cognitive impairments and support the causal clinical data models. It may also improve our knowledge of psychological disturbances and complex comorbidities to help design rehabilitation interventions and comprehensive frameworks in line with the “preventive medicine” policies.

Abstract Background Pharmacy interventions are a subset of public health interventions and its research is usually performed within the scope of a trial. The economic evaluation of pharmacy interventions requires certain considerations which have some similarities to those of public health interventions and to economic evaluations alongside trials. The objective of this research is to perform an overview of systematic reviews of economic evaluations of pharmacy services and triangulate results with recommendations for economic evaluations of both public health interventions and alongside trials. Methods (1) Exploratory review of recommendations on the economic evaluation of public health interventions, (2) exploratory review of recommendations for conducting economic evaluations alongside trials, (3) overview of systematic reviews of economic evaluations of pharmacy interventions (protocol registered with PROSPERO 2016 outlining information sources, inclusion criteria, appraisal of reviews and synthesis methods). Results Fourteen systematic reviews containing 75 index publications were included. Reviews reported favorable economic findings for 71% of studies with full economic evaluations. The types of economic analysis are diverse. Two critical quality domains are absent from most reviews. Key findings include the following: certain types of risk of bias, wider scope of study designs, and most economic quality criteria met but some issues unresolved or unclear. Triangulation revealed additional gaps. Limitations include choice of critical quality domains and potential biases in the overview process. Conclusions Economic evaluations of pharmacy-based public health interventions seem to follow most economic quality criteria, but there are still some issues in certain key areas to improve. These findings may assist in improving the design of pilot trials of economic evaluations in pharmacy, leading to robust evidence for payers. Based on the findings, we propose a methodological approach for the economic evaluation of pharmacy-based public health interventions. Systematic review registration PROSPERO CRD42016032768

Abstract Background BRCA1 associated-protein 1 (BAP1) tumor predisposition syndrome is associated with an increased risk for malignant mesotheliomas, uveal and cutaneous melanomas, renal cell carcinomas, and singular cutaneous lesions. The latter are referred to as BAP1-inactivated melanocytic tumors (BIMTs). When multiple BIMTs manifest, they are considered potential markers of germline BAP1 mutations. Case presentation Here, we report a novel pathogenic BAP1 germline variant in a family with a history of BIMTs, cutaneous melanomas, and mesotheliomas. We also describe singular pathological aspects of the patient’s BIMT lesions and their correlation with dermoscopic and reflectance confocal microscopy findings. Conclusions This knowledge is crucial for the recognition of BIMTs by dermatologists and pathologists, allowing the determination of appropriate management for high-risk patients, such as genetic investigations and screening for potentially aggressive tumors.

Abstract Background The skin is colonized by a large number of microorganisms, most of which are beneficial or harmless. However, disease states of skin have specific microbiome compositions that are different from those of healthy skin. Gut microbiome modulation through fecal transplant has been proven as a valid therapeutic strategy in diseases such as Clostridium difficile infections. Therefore, techniques to modulate the skin microbiome composition may become an interesting therapeutic option in diseases affecting the skin such as psoriasis or acne vulgaris. Methods Here, we have used mixtures of different skin microbiome components to alter the composition of recipient skin microbiomes. Results We show that after sequential applications of a donor microbiome, the recipient microbiome becomes more similar to the donor. After intervention, an initial week-long phase is characterized by the dominance of donor strains. The level of engraftment depends on the composition of the recipient and donor microbiomes, and the applied bacterial load. We observed higher engraftment using a multi-strain donor solution with recipient skin rich in Cutibacterium acnes subtype H1 and Leifsonia. Conclusions We have demonstrated the use of living bacteria to modulate skin microbiome composition.

Background: Narrow-band imaging (NBI) allows “in vivo” classification of colorectal polyps. Objectives: We evaluated the optical diagnosis by nonexpert community-based endoscopists in routine clinical practice, the impact of training, and whether the endoscopists could achieve the threshold for the “do not resect” policy. Methods: This was an observational study performed in two periods (P1 and P2). Endoscopists had no prior experience in NBI in P1 and applied the technique on a daily basis for 1 year before participation in P2. Lesions were classified by applying the NBI International Colorectal Endoscopic (NICE) and Workgroup serrAted polypS and Polyposis (WASP) classifications, simultaneously. Results: A total of 290 polyps were analyzed. The overall accuracy of optical diagnosis was 0.75 (95% CI 0.68–0.81) in P1, with an increase to 0.82 (95% CI 0.73–0.89) in P2 (p = 0.260). The accuracy of the NICE/WASP classifications to differentiate adenomatous from nonadenomatous histology was 0.78 (95% CI 0.72–0.84) in P1 and 0.86 (95% CI 0.77–0.92) in P2 (p = 0.164); assignments made with a high confidence level achieved statistical significance (13% improvement, 95% CI 3–22%; p = 0.022). The negative predictive value for adenomatous histology of diminutive rectosigmoid polyps was 81% (95% CI 64–93%) and 80% (95% CI 59–93%) in P1 and P2, respectively. Conclusions: Nonexpert endoscopists achieved moderate accuracy for real-time optical diagnosis of colorectal lesions with the NICE/WASP classifications. The overall performance of the endoscopists improved after sustained use of optical diagnosis, but did not achieve the standards for the implementation of the “do not resect” strategy.

This study aimed to quantify the external match loads (EMLs) of a Portuguese u-23 soccer team, competing at the highest national level for the age group, comparing players with different starting status throughout a competitive season and specific blocks. Thirty-five outfield soccer players were split into three groups for the entire season analysis and for each 3-month block, based on the percentage of games played as a starter. The three groups consisted of “starters” (≥55% of the games as a starter), “fringe” (30–54%), and “non-starters” (p < 0.05) were found for total distance (TD), exposure time, and the number of accelerations and decelerations between starters and non-starters throughout the season (d = 0.73 to 1.08), and within each block (d = 0.59 to 1.68). Differences were also found between starters and fringe players for the number of accelerations in Block 2 (p = 0.03; d = 0.69), and TD (p = 0.006; d = 1) and exposure time (p = 0.006; d = 0.95) in Block 3. Differences in the EML were almost always accompanied by large differences in game time. Our results highlight the differences in the EML of starters and non-starters, emphasizing the need for compensatory training, especially with players that obtain significantly less playing time, to prepare the players for match demands (e.g., high-intensity efforts such as sprinting, accelerations, and decelerations).

O objetivo do presente estudo é demonstrar a conformação do instituto da liquidação de sentença no novo Código de Processo Civil. O tipo de pesquisa empregado é operatório, acompanhado de técnicas bibliográfica e documental, pautado em método indutivo, que visa à análise crítica das normas relativas ao tema, para propiciar, como síntese geral, um estudo de aproveitamento na solução de problemas práticos verificados na praxe forense. O objetivo é tratar de algumas das questões mais polêmicas sobre o assunto à luz das novas disposições legais. Embora a sistemática procedimental e as hipóteses de cabimento da liquidação de sentença não tenham sido alteradas, algumas modificações demonstram a pertinência de revisitar o tema, em razão de sua relevância para a ciência processual.

Introduction: The potential therapeutic efficacy of real-time fMRI Neurofeedback has received increasing attention in a variety of psychological and neurological disorders and as a tool to probe cognition. Despite its growing popularity, the success rate varies significantly, and the underlying neural mechanisms are still a matter of debate. The question whether an individually tailored framework positively influences neurofeedback success remains largely unexplored.Methods: To address this question, participants were trained to modulate the activity of a target brain region, the visual motion area hMT+/V5, based on the performance of three imagery tasks with increasing complexity: imagery of a static dot, imagery of a moving dot with two and with four opposite directions. Participants received auditory feedback in the form of vocalizations with either negative, neutral or positive valence. The modulation thresholds were defined for each participant according to the maximum BOLD signal change of their target region during the localizer run.Results: We found that 4 out of 10 participants were able to modulate brain activity in this region-of-interest during neurofeedback training. This rate of success (40%) is consistent with the neurofeedback literature. Whole-brain analysis revealed the recruitment of specific cortical regions involved in cognitive control, reward monitoring, and feedback processing during neurofeedback training. Individually tailored feedback thresholds did not correlate with the success level. We found region-dependent neuromodulation profiles associated with task complexity and feedback valence.Discussion: Findings support the strategic role of task complexity and feedback valence on the modulation of the network nodes involved in monitoring and feedback control, key variables in neurofeedback frameworks optimization. Considering the elaborate design, the small sample size here tested (N = 10) impairs external validity in comparison to our previous studies. Future work will address this limitation. Ultimately, our results contribute to the discussion of individually tailored solutions, and justify further investigation concerning volitional control over brain activity.

The receptor for Colony Stimulating Factor 1 (CSF1), c-fms, is highly expressed on mature osteoclasts suggesting a role for this cytokine in regulating the function of these cells. Consistent with this idea, in vitro studies have documented a variety of effects of CSF1 in mature osteoclasts. To better define the role of CSF1 in these cells, we conditionally deleted c-fms in osteoclasts (c-fms-OC-/-) by crossing c-fmsflox/flox mice with mice expressing Cre under the control of the cathepsin K promoter. The c-fms-OC-/- mice were of normal weight and had normal tooth eruption. However, when quantified by DXA, bone mass was significantly higher in the spine and femur of female knock out mice and in the femurs of male knock out mice. MicroCT analyses of femurs showed that female c-fms-OC-/- mice had significantly increased trabecular bone mass with a similar trend in males and both sexes demonstrated significantly increased trabecular number and reduced trabecular spacing. Histomorphometric analysis of the femoral trabecular bone compartment demonstrated a trend towards increased numbers of osteoclasts, +26% in Noc/BPm and +22% in OcS/BS in the k/o animals but this change was not significant. However, when the cellular volume of osteoclasts was quantified, the c-fms-OC-/- cells were found to be significantly smaller than controls. Mature osteoclasts show a marked spreading response when exposed to CSF1 in a non-gradient fashion. However, osteoclasts freshly isolated from c-fms-OC-/- mice had a near complete abrogation of this response. C-fms-OC-/- mice treated with (1-34)hPTH 80 ng/kg/d in single daily subcutaneous doses for 29 days showed an attenuated anabolic response in trabecular bone compared to wild-type animals. Taken together, these data indicate an important non-redundant role for c-fms in regulating mature osteoclast function in vivo.

Smart greenhouse farming has emerged as one of the solutions to global food security, where farming productivity can be managed and improved in an automated manner. While it is known that plant development is highly dependent on the quantity and quality of light exposure, the specific impact of the different light properties is yet to be fully understood. In this study, using the model plant Arabidopsis, we systematically investigate how six different light properties (i.e., photoperiod, light offset, intensity, phase of dawn, duration of twilight and period) would affect plant development i.e., flowering time and hypocotyl (seedling stem) elongation using an established mathematical model of the plant circadian system relating light input to flowering time and hypocotyl elongation outputs for smart greenhouse application. We vary each of the light properties individually and then collectively to understand their effect on plant development. Our analyses show in comparison to the nominal value, the photoperiod of 18 hours, period of 24 hours, no light offset, phase of dawn of 0 hour, duration of twilight of 0.05 hour and a reduced light intensity of 1% are able to improve by at least 30% in days to flower (from 32.52 days to 20.61 days) and hypocotyl length (from 1.90 mm to 1.19mm) with the added benefit of reducing energy consumption by at least 15% (from 4.27 MWh/year to 3.62 MWh/year). These findings could provide beneficial solutions to the smart greenhouse farming industries in terms of achieving enhanced productivity while consuming less energy.

A expansão do cultivo da juta em território brasileiro liderada pelos imigrantes japoneses encontrou solo fértil nas várzeas dos Estados do Pará e Amazonas, levando o primeiro a ser responsável por um quarto da produção nacional na década de 1960. Este artigo tem como objetivo explicar tanto a expansão quanto a queda na produção por meio dos fatores institucionais, para tanto utiliza o arcabouço teórico da Nova Economia Institucional de Douglas North. Os resultados mostraram que mesmo as instituições e organizações que trouxeram incentivo à produção representaram também restrições à atividade, permanecendo a produção enraizada em antigos processos produtivos que limitaram o avanço tecnológico. Dessa forma, a inexistência de um arranjo institucional adequado ao desenvolvimento da atividade está no cerne do fracasso da cultura da juta no Estado.

A aproximação entre trabalho e educação pode ser identificada desde os estudos das comunidades primitivas, onde as tribos criavam métodos de produção de sua existência e desenvolviam processos que serviriam de ensinamentos para as novas gerações. A educação profissional tem avançado no Brasil, apesar de ainda focar em uma formação majoritariamente tecnicista e, portanto, minimizar as possibilidades de ampliação formativa. As mudanças no mundo do trabalho estão ocorrendo em uma velocidade nunca vista antes, o que torna um desafio pensar em práticas pedagógicas que aproximem o aluno da realidade atual. Diante desse desafio, o Projeto Laboratório de Prototipagem (LAB IFMaker) do IFCE apresenta-se como uma estratégia integradora da metodologia Learning By Doing com a implementação de laboratórios para serem utilizados na formação. Neste sentido, objetivou-se identificar potencialidades de inovação do Projeto Laboratório de Prototipagem Lab IFMaker em soluções criativas e eficientes nos processos de ensino do IFCE de modo a integrar a comunidade acadêmica. A pesquisa foi realizada com a abordagem qualitativa e o método estudo de caso. Na primeira fase do percurso investigativo, deram-se os estudos dos fundamentos teóricos acerca da categoria formação para o mundo do trabalho. Posteriormente, tendo o projeto Lab IFMaker do IFCE como objeto de estudo, caracterizaram-se os pressupostos multidisciplinares e integradores do fenômeno em análise.

The main goal of the present research is to propose an integrated methodology to address the fatigue performance of topology optimized components, produced by additive manufacturing. The main steps of the component design will be presented, specially the methods and parameters applied to the topology optimization and the post-smoothing process. The SIMP method was applied in order to obtain a lighter component and a suitable stiffness for the desired application. In addition, since residual stresses are intrinsic to every metallic additive manufacturing process, the influence of those stresses will be also analyzed. The Laser Powder Bed Fusion was numerically simulated aiming at evaluating the residual stresses the workpiece during the manufacturing process and to investigate how they could influence the fatigue behavior of the optimized component. The effect of the built orientation of the workpiece on the residual stresses at some selected potential critical points are evaluated. The final design solution presented a stiffness/volume ratio nearly 6 times higher when compared to the initial geometry. By choosing the built orientation, it is possible impact favorably in the fatigue life of the component.

This paper describes the development of three main functionalities for a domestic mobile service robot and an automatic benchmarking system used for the systematic performance evaluation of the robot’s functionalities. Three main robot functionalities are addressed: (1) People Perception, (2) People Following and (3) Pick and Placing, where the hardware and software systems developed for each functionality are described and demonstrated on an actual mobile service robot, with the goal of providing assistance to an elderly person inside the house. Furthermore, a set of innovative benchmarks and an automatic performance evaluation system are proposed and used to evaluate the performance of the developed functionalities. These benchmarks are now made publicly available and is part of the European Robotics League (ERL)-Consumer to systematically evaluate the performance of service robot solutions at different testbeds around Europe.