Enhancing declarative process models with DMN decision logic

Modeling dynamic, human-centric, non-standardized and knowledge-intensive business processes with imperative process modeling approaches is very challenging. Declarative process modeling approaches are more appropriate for these processes, as they offer the run-time flexibility typically required in these cases. However, by means of a realistic healthcare process that falls in the aforementioned category, we demonstrate in this paper that current declarative approaches do not incorporate all the details needed. More specifically, they lack a way to model decision logic, which is important when attempting to fully capture these processes. We propose a new declarative language, Declare-R-DMN, which combines the declarative process modeling language Declare-R with the newly adopted OMG standard Decision Model and Notation. Aside from supporting the functionality of both languages, Declare-R-DMN also creates bridges between them. We will show that using this language results in process models that encapsulate much more knowledge, while still offering the same flexibility

Inhibition of HIV cell-to-cell fusion by antiretroviral drugs and neutralizing antibodies

Poster presented at the 7th iMed.ULisboa Postgraduate Students Meeting. Lisbon, 15 July 2015"Inhibition of HIV cell entry by antiretroviral drugs and neutralizing antibodies (NAbs) is typically measured in assays where cell-free virions enter reporter cell lines. However, direct Env-mediated cell-to-cell transmission is a major mechanism of HIV infection that also needs to be targeted. In this work we aimed to determine the ability of anti-HIV compounds in clinical or research use to inhibit HIV mediated cell-to-cell fusion (syncytia formation)."Fundação para a Ciência e a Tecnologia - Portugal ; European Unio

Função Respiratória na Criança em Idade Pré-Escolar

A avaliação funcional respiratória é fundamental para a avaliação do doente com diversas patologias, nomeadamente respiratória, sendo corrente o seu uso em adultos e em crianças em idade escolar. Embora para o lactente tenham sido investigados vários métodos nas últimas décadas, a criança em idade pré-escolar tem permanecido como inacessível, pela necessidade de colaboração e pela impraticabilidade de sedação. Os autores descrevem os avanços em avaliação funcional respiratória nos últimos anos, nesta faixa etária, nas técnicas de espirometria e pletismografia, explicitando a sua fundamentação teórica, metodologia e aplicabilidade

Chlamydia trachomatis infection in patients selected for HPV detection

Background: The significance of the association between the human papillomavirus (HPV) and other sexually transmitted infections in the development of cervical, penile or anal neoplasias has been investigated, and the more consistent data have pointed to an association with Chlamydia trachomatis. In Portugal, the lack of information on STI precludes any knowledge on this subject. Objective: To determine CT infection in a group of individuals selected for HPV detection in the major Portuguese STD clinic. Methods: This opportunistic screening comprehended 177 outpatients (148 women, 29 men; age: 16-61 years) suspected of HPV infection (warts, abnormal histology) between 2008 and 2010. Demographic and sexual behaviour data and a full medical history were obtained at enrolment. Genital samples (cervical, vulvar, vaginal, penile or anal) were collected from all the subjects. HPV DNA was detected by CLART HPV2 assay, which allowed the detection of 35 genotypes. CT DNA was detected by Cobas 4800. Results and Discussion: Overall, 84.5% of the individuals had at least one of the infections. Evidencing an excellent correlation with clinical signs, HPV infection was detected in 68.2% of the women and in 75.9% of the men, where CT positivity was 10.1% and 13.8%, respectively. Coinfection was observed in 8.9% of the women and in 13.8% of the men. No correlation with HPV or CT genotypes could be established. HPV infection was more frequent in CT negative (87.1%) than in CT positive women (13.8%), and the same was observed for men (81.8% versus 18.2%). Full results will be presented and discussed. Conclusions: No correlation between HPV-CT coinfection, and clinical signs was observed. However, further long-term studies are needed to elucidate the effects of HPV-CT coinfection in the clinical history of the infected patient, which would greatly contribute towards a better management of patients

The ACCENT-protocol: a framework for benchmarking and model evaluation

We summarise results from a workshop on “Model Benchmarking and Quality Assurance” of the EU-Network of Excellence ACCENT, including results from other activities (e.g. COST Action 732) and publications. A formalised evaluation protocol is presented, i.e. a generic formalism describing the procedure of how to perform a model evaluation. This includes eight steps and examples from global model applications which are given for illustration. The first and important step is concerning the purpose of the model application, i.e. the addressed underlying scientific or political question. We give examples to demonstrate that there is no model evaluation per se, i.e. without a focused purpose. Model evaluation is testing, whether a model is fit for its purpose. The following steps are deduced from the purpose and include model requirements, input data, key processes and quantities, benchmark data, quality indicators, sensitivities, as well as benchmarking and grading. We define “benchmarking” as the process of comparing the model output against either observational data or high fidelity model data, i.e. benchmark data. Special focus is given to the uncertainties, e.g. in observational data, which have the potential to lead to wrong conclusions in the model evaluation if not considered carefully.publishe

Estrogen-related genes and postmenopausal osteoporosis risk

Background To date, more than 150 candidate genes related to osteoporosis have been described, but osteoporosis has increasingly been considered a polygenic disease modulated by environmental factors. It is thought that osteoporosis predisposition, pathology, and treatment response depend on the interaction between different genes or between genes and environmental factors. Objective The aim of this study was to evaluate the relationship between the presence of single nucleotide polymorphisms (SNPs) in the estrogen metabolic pathway and the development of osteoporosis and to determine whether this relationship is monogenic or whether interactions between genes exist. Materials and methods A multicentric study with 1980 postmenopausal Spanish women in fi ve Spanish communities was conducted. The women completed a specifi c questionnaire that inquired about risk factors for osteoporosis. Data on participants ’ bone mineral density were obtained with dual-energy X-ray densitometers, and genetic data were obtained from frozen peripheral blood. Results The digenic protection combinations indicated involvement of the wild-type genotype (WT) of the 3 UTR marker for the CYP19A1 gene, the IVS4 marker of the same gene, and the BMP15 and FSHR genes. Among patients who carried two or more of the genotypes considered ‘ risky ’ , the triple combination among markers of the ESR2 and NRIP1 genes with any of the two mutations of the analyzed markers of the BMP15 gene gave a mean T -score value of 2.32 0.91 ( p 0.02). Conclusion Variants of the new candidate genes ( NRIP and BMP15 ) can predispose patients to osteoporosis

Lymphocyte Subpopulations in Sjögren’s Syndrome Are Distinct in Anti-SSA-Positive Patients and Related to Disease Activity

Objectives: Sjögren's syndrome (SjS) patients exhibit great phenotypical heterogeneity, reinforced by the positiveness of anti-SSA antibody. We aimed to evaluate lymphocyte subpopulations in SSA-positive (SSA+SjS) and SSA-negative (SSA-SjS) SjS patients, Sicca patients, and healthy controls (HC), and to investigate associations between lymphocyte subpopulations and disease activity in SjS. Methods: According to the fulfilment of the ACR/EULAR 2016 classification criteria, patients were included as SjS or as Sicca. HC were selected from the Ophthalmology outpatient clinic. Lymphocyte subpopulations were characterized by flow cytometry. Statistical analysis was performed with GraphPad PrismTM, with statistical significance concluded if p < 0.05. Results: We included 53 SjS patients (38 SSA+ and 15 SSA-), 72 Sicca, and 24 HC. SSA+SjS patients presented increased IL-21+CD4+ and CD8+ T cells compared to Sicca and HC, whereas compared to SSA-SjS patients, only IL-21+CD4+ T cell percentages were increased and Tfh17 percentages and numbers were decreased. Compared to Sicca and HC, SSA+SjS patients had higher levels of CD24HiCD38Hi B cells, naïve B cells, and IgM-/+CD38++ plasmablasts, and lower levels of memory B cells, including CD24HiCD27+ B cells. SSA+SjS patients with clinically active disease had positive correlations between ESSDAI and IL-21+CD4+ (p = 0.038, r = 0.456) and IL-21+CD8+ T cells (p = 0.046, r = 0.451). Conclusions: In SjS, a distinct lymphocyte subset distribution profile seems to be associated with positive anti-SSA. Moreover, the association between ESSDAI and IL-21+CD4+ and IL-21+CD8+ (follicular) T cells in SSA+SjS patients suggests the involvement of these cells in disease pathogenesis and activity, and possibly their utility for the prognosis and assessment of response to therapy. Key Points • SSA+SjS patients have a pronounced naïve/memory B cell imbalance. • SSA+SjS patients have more active disease associated with IL-21+CD4+ and IL-21+CD8+ follicular T cell expansion. • IL-21+CD4+ and IL-21+CD8+ T cell quantification may be useful for the prognosis and assessment of response to therapy.info:eu-repo/semantics/publishedVersio

The synergetic effect from the combination of different adsorption resins in batch and semi-continuous cultivations of S. Cerevisiae cell factories to produce acetylated Taxanes precursors of the anticancer drug Taxol

In situ product recovery is an efficient way to intensify bioprocesses as it can perform adsorption of the desired natural products in the cultivation. However, it is common to use only one adsorbent (liquid or solid) to perform the product recovery. For this study, the use of an in situ product recovery method with three combined commercial resins (HP-20, XAD7HP, and HP-2MG) with different chemical properties was performed. A new yeast strain of Saccharomyces cerevisiae was engineered using CRISPR Cas9 (strain EJ2) to deliver heterologous expression of oxygenated acetylated taxanes that are precursors of the anticancer drug Taxol ® (paclitaxel). Microscale cultivations using a definitive screening design (DSD) were set to get the best resin combinations and concentrations to retrieve high taxane titers. Once the best resin treatment was selected by the DSD, semi-continuous cultivation in high throughput microscale was performed to increase the total taxanes yield up to 783 ± 33 mg/L. The best T5α-yl Acetate yield obtained was up to 95 ± 4 mg/L, the highest titer of this compound ever reported by a heterologous expression. It was also observed that by using a combination of the resins in the cultivation, 8 additional uncharacterized taxanes were found in the gas chromatograms compared to the dodecane overlay method. Lastly, the cell-waste reactive oxygen species concentrations from the yeast were 1.5-fold lower in the resin's treatment compared to the control with no adsorbent aid. The possible future implications of this method could be critical for bioprocess intensification, allowing the transition to a semi-continuous flow bioprocess. Further, this new methodology broadens the use of different organisms for natural product synthesis/discovery benefiting from clear bioprocess intensification advantages

Efecto del drenaje ácido sobre el fraccionamiento de tierras raras ligeras en sedimentos: un caso de estudio en el estuario de los ríos Tinto y Odiel

The effect of acid drainage on light rare earth elements (LREE) has been studied in the estuarine sediment of the Tinto and Odiel system, where the fluvial and marine water mixing cause an important pH and chlorinity gradient inside. Due to the high influence of pH over the LREE partitioning from dissolved toparticulate phases, an anomalous behaviour has been found on La content in these sediments. Large removal of LREE takes place at low chlorinity zones in unaffected estuaries, but in the studied system this natural process is moved out the outer zones of the estuary. So, the relative La depletion in the estuarine mixing zone is due to the low pH values (< 6) that prevents LREE removal in low chlorinity zones. Once the acid neutralization (pH ~ 7) occurs, some La enrichment can be observed in sediments of the marine estuary.Versión de edito