60 research outputs found

    Um algoritmo evolutivo para a programação de projetos multi-modos com nivelamento de recursos limitado

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    Tese (doutorado) - Universidade Federal de Santa Catarina, Centro TecnologicoO problema de programação de projetos com restrição de recursos, Ă© considerado um dos problemas mais desafiantes. A busca de soluçÔes atravĂ©s de abordagens analĂ­ticas tem alcançado relativo sucesso somente em problemas de pequeno porte. Desta forma, esforços vem sendo realizados na procura de soluçÔes mais robustas atravĂ©s de abordagens heurĂ­sticas. Este trabalho apresenta um modelo que utiliza os algoritmos genĂ©ticos como abordagem heurĂ­stica para resolver o problema de alocação de recursos limitados em ambientes de mĂșltiplos modos. AlĂ©m disto, o conceito de nivelamento de recursos Ă© incorporado ao procedimento como um mecanismo guia na busca de uma solução de mĂ­nima duração, com padrĂ”es de flutuação dos recursos utilizados de alguma forma reduzido

    Inactivation of nuclear factor-Y inhibits vascular smooth muscle cell proliferation and neointima formation

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    OBJECTIVE: Atherosclerosis and restenosis are multifactorial diseases associated with abnormal vascular smooth muscle cell (VSMC) proliferation. Nuclear factor-Y (NF-Y) plays a major role in transcriptional activation of the CYCLIN B1 gene (CCNB1), a key positive regulator of cell proliferation and neointimal thickening. Here, we investigated the role of NF-Y in occlusive vascular disease. APPROACH AND RESULTS: We performed molecular and expression studies in cultured cells, animal models, and human tissues. We find upregulation of NF-Y and cyclin B1 expression in proliferative regions of murine atherosclerotic plaques and mechanically induced lesions, which correlates with higher binding of NF-Y to target sequences in the CCNB1 promoter. NF-YA expression in neointimal lesions is detected in VSMCs, macrophages, and endothelial cells. Platelet-derived growth factor-BB, a main inductor of VSMC growth and neointima development, induces the recruitment of NF-Y to the CCNB1 promoter and augments both CCNB1 mRNA expression and cell proliferation through extracellular signal-regulated kinase 1/2 and Akt activation in rat and human VSMCs. Moreover, adenovirus-mediated overexpression of a NF-YA-dominant negative mutant inhibits platelet-derived growth factor-BB-induced CCNB1 expression and VSMC proliferation in vitro and neointimal lesion formation in a mouse model of femoral artery injury. We also detect NF-Y expression and DNA-binding activity in human neointimal lesions. CONCLUSIONS: Our results identify NF-Y as a key downstream effector of the platelet-derived growth factor-BB-dependent mitogenic pathway that is activated in experimental and human vasculoproliferative diseases. They also identify NF-Y inhibition as a novel and attractive strategy for the local treatment of neointimal formation induced by vessel denudation.This study was funded by the Spanish Ministry of Economy and Competiveness (MINECO; grants SAF2010-16044, SAF200911949), Instituto de Salud Carlos III (ISCIII; grants RD12/0042/0021, RD12/0042/0028, RD12/0042/0053), and the Dr LĂ©on Dumont Prize 2010 by the Belgian Society of Cardiology (to Vicente AndrĂ©s). Patricia FernĂĄndez received salary support from ISCIII and Carlos Silvestre-Roig from FundaciĂłn Mario Losantos del Campo and FundaciĂłn Ferrer para la InvestigaciĂłn. Óscar M. Pello and Ricardo RodrĂ­guez-Calvo hold a Juan de la Cierva contract from MINECO. Vanesa Esteban is an investigator of the Sara Borell program from ISCIII (CD06/00232). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by MINECO and Pro-CNIC Foundation.S

    Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

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    Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

    Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

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    : The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSSŸ v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

    The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

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    Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

    MAGIC and H.E.S.S. detect VHE gamma rays from the blazar OT081 for the first time: a deep multiwavelength study

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    https://pos.sissa.it/395/815/pdfPublished versio

    Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

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    Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≄ II, EF ≀35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

    Politica para a substituição da frota de transporte rodoviario de carga

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    Dissertação (mestrado) - Universidade Federal de Santa Catarina. Centro TecnologicoAs técnicas de Engenharia EconÎmica disponíveis para a anålise de problemas de substituição, consideram

    Problema de programação da produção um esquema de classificação

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    Muitas vezes, não é simples encontrar uma classificação exata para os problemas de programação, não somente porque existem diferentes versÔes para um dado problema, mas, porque vårios procedimentos para uma questão particular, são caracterizados por premissas diferentes e limitaçÔes de aplicação dos modelos desenvolvidos. O objetivo deste artigo é delinear uma classificação ampla que permita estabelecer o sentido, direção e perspectiva de pesquisas conduzidas na årea. O trabalho não tem a intenção de dar um levantamento exaustivo da literatura de programação da produção, que pode ser encontrado em vårios outros trabalhos de revisão.<br>It is the purpose of this article to review the various solutions that have been proposed for the production scheduling problem. An attempt is made to give a classification scheme to categorize the existing procedures that allow to point out potential future courses of development. Emphasis is placed on the basic assumptions involved in each production sequencing problem rather than to approaches used to obtain a solution

    Resolving the origin of very-high-energy gamma-ray emission from the PeVatron candidate SNR G106.3+2.7 using MAGIC telescopes

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    The supernova remnant (SNR) G106.3+2.7 associated with a 100 TeV gamma-ray source reported by HAWC, Tibet ASÎł, and LHAASO Collaborations is one of the promising PeVatron candidates. Because the SNR contains an energetic pulsar wind nebula (PWN) dubbed Boomerang powered by the pulsar PSR J2229+6114, it is unclear whether the gamma-ray emission originates from the SNR or PWN complex and whether it is caused by hadronic or leptonic processes. We observed gamma rays above 200 GeV in the vicinity of the SNR G106.3+2.7 using the MAGIC telescopes for total ∌ 120 hours between May 2017 and August 2019 with an angular resolution of 0.07– 0.10 degrees, achieving an unprecedented exposure for this object at these energies. An extended gamma-ray emission spatially correlated with the radio continuum emission at the head and tail of SNR G106.3+2.7 was detected using the MAGIC telescopes. We found a significant gamma-ray emission above 5.65 TeV only from the SNR tail region, while no significant emission in the same band is found at the SNR head region containing the Boomerang PWN. Therefore, the gamma rays above 10 TeV detected with the air shower experiments are, likely, mainly emitted from the SNR tail region. In this presentation, we discuss the morphology of the gamma-ray emission from this complex region and attempt self-consistent multi-wavelength modeling of the energy spectrum
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