Combining filter method and dynamically dimensioned search for constrained global optimization

In this work we present an algorithm that combines the filter technique and the dynamically dimensioned search (DDS) for solving nonlinear and nonconvex constrained global optimization problems. The DDS is a stochastic global algorithm for solving bound constrained problems that in each iteration generates a randomly trial point perturbing some coordinates of the current best point. The filter technique controls the progress related to optimality and feasibility defining a forbidden region of points refused by the algorithm. This region can be given by the flat or slanting filter rule. The proposed algorithm does not compute or approximate any derivatives of the objective and constraint functions. Preliminary experiments show that the proposed algorithm gives competitive results when compared with other methods.The first author thanks a scholarship supported by the International Cooperation Program CAPES/ COFECUB at the University of Minho. The second and third authors thanks the support given by FCT (Funda¸c˜ao para Ciˆencia e Tecnologia, Portugal) in the scope of the projects: UID/MAT/00013/2013 and UID/CEC/00319/2013. The fourth author was partially supported by CNPq-Brazil grants 308957/2014-8 and 401288/2014-5.info:eu-repo/semantics/publishedVersio

Filter-based stochastic algorithm for global optimization

We propose the general Filter-based Stochastic Algorithm (FbSA) for the global optimization of nonconvex and nonsmooth constrained problems. Under certain conditions on the probability distributions that generate the sample points, almost sure convergence is proved. In order to optimize problems with computationally expensive black-box objective functions, we develop the FbSA-RBF algorithm based on the general FbSA and assisted by Radial Basis Function (RBF) surrogate models to approximate the objective function. At each iteration, the resulting algorithm constructs/updates a surrogate model of the objective function and generates trial points using a dynamic coordinate search strategy similar to the one used in the Dynamically Dimensioned Search method. To identify a promising best trial point, a non-dominance concept based on the values of the surrogate model and the constraint violation at the trial points is used. Theoretical results concerning the sufficient conditions for the almost surely convergence of the algorithm are presented. Preliminary numerical experiments show that the FbSA-RBF is competitive when compared with other known methods in the literature.The authors are grateful to the anonymous referees for their fruitful comments and suggestions.The first and second authors were partially supported by Brazilian Funds through CAPES andCNPq by Grants PDSE 99999.009400/2014-01 and 309303/2017-6. The research of the thirdand fourth authors were partially financed by Portuguese Funds through FCT (Fundação para Ciência e Tecnologia) within the Projects UIDB/00013/2020 and UIDP/00013/2020 of CMAT-UM and UIDB/00319/2020

Evidence That Lipopolisaccharide May Contribute to the Cytokine Storm and Cellular Activation in Patients with Visceral Leishmaniasis

Visceral leishmaniasis (VL) affects organs rich in lymphocytes, being characterized by intense Leishmania-induced T-cell depletion and reduction in other hematopoietic cells. In other infectious and non-infectious diseases in which the immune system is affected, such as HIV-AIDS and inflammatory bowel disease, damage to gut-associated lymphocyte tissues occurs, enabling luminal bacteria to enter into the circulation. Lipopolisaccharide (LPS) is a bacterial product that stimulates macrophages, leading to the production of pro-inflammatory cytokines and other soluble factors such as MIF, which in turn activate lymphocytes. Continuous and exaggerated stimulation causes exhaustion of the T-cell compartment, contributing to immunosuppression

Tratamento com radio e quimioterapia do carcinoma epidermóide do canal anal: experiência do hospital Barão de Lucena Radiochemotherapy for squamous cell carcinoma of the anal canal: Barao de Lucena hospital experience

Objetivos: Apresentar os resultados e analisar as variáveis implicadas no tratamento e prognóstico do carcinoma epidermóide do canal anal tratado através da radio e quimioterapia no Hospital Barão de Lucena-SUS-PE. Metodologia: Análise dos prontuários de pacientes com diagnóstico de câncer do canal anal submetidos a tratamento radioquimioterápico. O período de acompanhamento foi de junho de 1989 a junho de 2005. Foram incluídos os pacientes com diagnóstico histológico de câncer de canal anal, enquadrados nos estadios I, II, IIIa e IIIb, submetidos a dois ciclos de quimioterapia com 5-fluorouracil (5-FU) na dose de 1g/m²/dia em infusão contínua de 96 horas e cisplatino na dose de 100mg/m² administrado em 6 horas no segundo dia de infusão de cada ciclo, administrados na primeira e terceira semanas do esquema de tratamento radioterápico. Resultados: Avaliamos 108 prontuários de pacientes que preencheram os critérios do protocolo. O tempo médio de seguimento foi de 51 meses (1-182 meses). Houve predomínio do gênero feminino (81,5% dos pacientes). A idade variou de 33 a 83 anos (média de 59 anos). O tipo histológico mais freqüente foi o carcinoma de células escamosas (80,6% dos casos). Em 21 pacientes, foi diagnosticado carcinoma basalóide. Quanto ao grau de diferenciação, prevaleceu o tipo moderadamente diferenciado (61% dos pacientes com carcinoma de células escamosas). O índice de resposta inicial completa foi de 89,8%. Onze pacientes persistiram com tumor após o tratamento radio e quimioterápico. O índice de resposta inicial completa foi menor nos estadios IIIa e IIIb em relação aos estadios I e II com significância estatística (p<0,05). 14 pacientes evoluíram com recidiva tumoral, oito com recidiva local (7,4%) e seis (5,5%) com recidiva linfática e à distância. CONCLUSÕES: O tratamento radioquimioterápico exclusivo do carcinoma epidermóide do canal anal, tem índice de resposta completo bastante elevado com morbidade aceitável. O tratamento cirúrgico ainda tem seu valor nos casos de persistência da lesão e/ou de recidiva local, com resultados satisfatórios.<br>Objectives: To present the results and analyze the variables involved in the treatment and prognosis of squamous cell carcinoma of the anal canal treated by radiotherapy and chemotherapy at the Hospital Barao de Lucena-SUS-PE. Methodology: Analysis of medical records of patients diagnosed with anal cancer treated by chemoradiation. The monitoring period was from June 1989 to June 2005. We included patients with histologically confirmed cancer of the anal canal, framed in stages I, II, IIIa and IIIb, underwent two cycles of chemotherapy with 5-fluorouracil (5-FU) at a dose of 1g / m² / day continuous infusion 96 hours and cisplatin at a dose of 100 mg / m² administered at 6 hours the second day of infusion of each cycle, administered on the first and third weeks of radiotherapy treatment regimen. Results: We evaluated records of 108 patients who met the criteria of the protocol. The mean follow-up was 51 months (1-182 months). There were more females (81.5% of patients). The age ranged from 33 to 83 years (mean 59 years). The most common histological type was squamous cell carcinoma (80.6% of cases). In 21 patients, was diagnosed Basaloid carcinoma. Regarding the degree of differentiation, the most prevalent type was moderately differentiated (61% of patients with squamous cell carcinoma). The rate of initial complete response was 89.8%. Eleven patients had persistent tumor after radiotherapy and chemotherapy. The initial response rate was lower in complete stages IIIa and IIIb compared to stages I and II with statistical significance (p <0.05). 14 patients developed recurrence, eight with local recurrence (7.4%) and six (5.5%) with lymphatic recurrence and distance. CONCLUSIONS: The chemoradiation treatment of unique cell carcinoma of the anal canal, have complete response rate very high with acceptable morbidity. Surgical treatment still has its value in cases of persistent injury and / or local recurrence, with satisfactory results

Diagnostic classification of childhood cancer using multiscale transcriptomics.

Acknowledgements: The KiCS program is supported by the Garron Family Cancer Centre at The Hospital for Sick Children through funding from the SickKids Foundation. A.H. received funding from the Canadian Institutes for Health Research (grant no. 162267) and is the Tier 1 Canada Research Chair in Rare Childhood Brain Tumors. D.M. is supported by the CIBC Children’s Foundation Chair in Child Health Research. A.S. is partially supported by an Early Researcher Award from the Ontario Ministry of Research and Innovation; by the Canada Research Chair in Childhood Cancer Genomics; and by funding from the V Foundation and the Robert J. Arceci Innovation Award from the St. Baldrick’s Foundation. We would like to thank the Centre for Applied Genomics, The Hospital for Sick Children, for assistance with RNA sequencing and the Treehouse Childhood Cancer Initiative, University of California, Santa Cruz, for access to their public data repository.The causes of pediatric cancers' distinctiveness compared to adult-onset tumors of the same type are not completely clear and not fully explained by their genomes. In this study, we used an optimized multilevel RNA clustering approach to derive molecular definitions for most childhood cancers. Applying this method to 13,313 transcriptomes, we constructed a pediatric cancer atlas to explore age-associated changes. Tumor entities were sometimes unexpectedly grouped due to common lineages, drivers or stemness profiles. Some established entities were divided into subgroups that predicted outcome better than current diagnostic approaches. These definitions account for inter-tumoral and intra-tumoral heterogeneity and have the potential of enabling reproducible, quantifiable diagnostics. As a whole, childhood tumors had more transcriptional diversity than adult tumors, maintaining greater expression flexibility. To apply these insights, we designed an ensemble convolutional neural network classifier. We show that this tool was able to match or clarify the diagnosis for 85% of childhood tumors in a prospective cohort. If further validated, this framework could be extended to derive molecular definitions for all cancer types

FDR-controlled metabolite annotation for high-resolution imaging mass spectrometry

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