Experimental designs for environmental valuation with choice-experiments: A Monte Carlo investigation

We review the practice of experimental design in the environmental economics literature concerned with choice experiments. We then contrast this with advances in the field of experimental design and present a comparison of statistical efficiency across four different experimental designs evaluated by Monte Carlo experiments. Two different situations are envisaged. First, a correct a priori knowledge of the multinomial logit specification used to derive the design and then an incorrect one. The data generating process is based on estimates from data of a real choice experiment with which preference for rural landscape attributes were studied. Results indicate the D-optimal designs are promising, especially those based on Bayesian algorithms with informative prior. However, if good a priori information is lacking, and if there is strong uncertainty about the real data generating process - conditions which are quite common in environmental valuation - then practitioners might be better off with conventional fractional designs from linear models. Under misspecification, a design of this type produces less biased estimates than its competitors

Preclinical Modelling of PDA: Is Organoid the New Black?

Pancreatic ductal adenocarcinoma (PDA) is a malignancy of the exocrine pancreas with the worst prognosis among all solid tumours, and soon to become the second leading cause of cancer-related deaths. A more comprehensive understanding of the molecular mechanisms underlying this disease is crucial to the development of diagnostic tools as well as to the identification of more effective therapies. High-frequency mutations in PDA occur in "undruggable" genes, and molecular subtyping based on bulk transcriptome analysis does not yet nominate valid therapeutic intervention strategies. Genome-wide sequencing studies have also demonstrated a considerable intra- and inter-patient's genetic heterogeneity, which further complicate this dire scenario. More than in other malignancies, functionalization of the PDA genome and preclinical modelling at the individual patient level appear necessary to substantially improve survival rates for pancreatic cancer patients. Traditional human PDA models, including monolayer cell cultures and patient-derived xenografts, have certainly led to valuable biological insights in the past years. However, those model systems suffer from several limitations that have contributed to the lack of concordance between preclinical and clinical studies for PDA. Pancreatic ductal organoids have recently emerged as a reliable culture system to establish models from both normal and neoplastic pancreatic tissues. Pancreatic organoid cultures can be efficiently generated from small tissue biopsies, which opens up the possibility of longitudinal studies in individual patients. A proof-of-concept study has demonstrated that patient-derived PDA organoids are able to predict responses to conventional chemotherapy. The use of this three-dimensional culture system has already improved our understanding of PDA biology and promises to implement precision oncology by enabling the alignment of preclinical and clinical platforms to guide therapeutic intervention in PDA

Effects of Inhalation of Thermal Water on Exhaled Breath Condensate in Chronic Obstructive Pulmonary Disease

Background: Inhalation of thermal water (TW) is traditionally used as part of the treatment of chronic obstructive pulmonary disease (COPD), but its benefit and mechanisms are controversial. We previously observed a reduced proportion of neutrophils in induced sputum after treatment with TW. Objectives: The aim of this study was to determine whether inhalation of TW in COPD patients is associated with biochemical changes of airway lining fluid, including a reduction in the neutrophil chemoattractant leukotriene B4 (LTB4). Methods: Thirteen COPD patients were randomly assigned to receive a 2-week course of TW and normal saline inhalation in a cross-over, single-blind study design. Exhaled breath condensate (EBC) was collected before and after treatments. LTB4 concentrations in EBC were determined by ELISA, and EBC pH was measured before and after argon deaeration. Results: No significant differences in LTB4 concentrations in EBC were detected with either treatment. A significant decrease in pH of non-deaerated EBC was observed after a standard course of TW (median 7.45, interquartile range 6.93–7.66, vs. median 6.99, interquartile range 6.57–7.19; p = 0.05), which disappeared after argon deaeration. Conclusions: There is no evidence that TW treatment affects LTB4 concentration in EBC. The results of EBC pH measurements suggest that TW inhalation induces an imbalance of volatile components of the buffer system in airway lining fluid

Proposta de validação de metodologia de análise de argumentos escritos de acordo com o TAP

A argumentação vem sendo tratada como um elemento da alfabetização científica. A análise \ud de argumentos pode ser encontrada em diferentes pesquisas da área de ensino de ciências. \ud Uma ferramenta amplamente utilizada é o padrão de argumentação de Toulmin (TAP), \ud adaptado de outra área de conhecimento, que tem sido utilizado para reestruturar textos de \ud alunos de maneira próspera. Uma vez que a metodologia proposta por Toulmin é de \ud construção de argumentos, entendemos que a reestruturação de um texto já anunciado precisa \ud ser reescrito no formato de TAP, portanto, precisa de uma metodologia própria. Propomos \ud uma metodologia para a análise de argumentos escritos que inclui a triangulação por pares, a \ud correção conceitual e a contextualização dos trechos dos textos a serem analisados. \ud Acreditamos que a proposição de uma metodologia é útil para a área já que não encontramos \ud descrições detalhadas de uso do TAP.Argumentation is considered a feature of scientific literacy. Argumentation analysis can be \ud found in several researches in science education field. A widely used argumentation analysis \ud tool is Toulmin’s argumentation pattern (TAP), adapted from another knowledge area, which \ud has been used to restructure students texts in a prosper way. Once Toulmin’s proposition \ud mean to help building arguments, we think that the restructure process of a text already \ud written into TAP needs a methodology of its own. We suggest a methodology to restructure \ud written texts that includes a peer review, a conceptual correction and also a contextualization \ud of the fragments analyzed. We believe that this methodology is useful for this research field \ud once there are no descriptions like this in TAP literature

Accuracy of magnetic resonance imaging to identify pseudocapsule invasion in renal tumors

Purpose: To evaluate accuracy of MRI in detecting renal tumor pseudocapsule (PC) invasion and to propose a classification based on imaging of PC status in patients with renal cell carcinoma. Methods: From January 2017 to June 2018, 58 consecutive patients with localized renal cell carcinoma were prospectively enrolled. MRI was performed preoperatively and PC was classified, according to its features, as follows: MRI-Cap 0 (absence of PC), MRI-Cap 1 (presence of a clearly identifiable PC), MRI-Cap 2 (focally interrupted PC), and MRI-Cap 3 (clearly interrupted and infiltrated PC). A 3D image reconstruction showing MRI-Cap score was provided to both surgeon and pathologist to obtain complete preoperative evaluation and to compare imaging and pathology reports. All patients underwent laparoscopic partial nephrectomy. In surgical specimens, PC was classified according to the renal tumor capsule invasion scoring system (i-Cap). Results: A concordance between MRI-Cap and i-Cap was found in 50/58 (86%) cases. ρ coefficient for each MRI-cap and iCap categories was: MRI-Cap 0: 0.89 (p < 0.0001), MRI-Cap1: 0.75 (p < 0.0001), MRI-Cap 2: 0.76 (p < 0.0001), and MRI-Cap3: 0.87 (p < 0.0001). Sensitivity, specificity, positive predictive value, negative predictive value, and AUC were: MRI-Cap 0: Se 97.87% Spec 83.3%, PPV 95.8%, NPV 90.9%, and AUC 90.9; MRI-Cap 1: Se 77% Spec 95.5%, PPV 83.3%, NPV 93.5%, and AUC 0.86; MRI-Cap 2- iCap 2: Se 88% Spec 90%, PPV 79%, NPV 95%, and AUC 0.89; MRI-Cap 3: Se 94% Spec 95%, PPV 88%, NPV 97%, and AUC 0.94. Conclusions: MRI-Cap classification is accurate in evaluating renal tumor PC features. PC features can provide an imaging-guided landmark to figure out where a minimal margin could be preferable during nephron-sparing surgery

Mismatch repair gene defects in sporadic colorectal cancer enhance immune surveillance

Background: There is evidence that colorectal cancers (CRC) with DNA mismatch repair deficiency (MMR-D) are associated with a better prognosis than the generality of large bowel malignancies. Since an active immune surveillance process has been demonstrated to influence CRC outcome, we investigated whether MMR-D can enhance the immune response in CRC. Patients and Methods: A group of 113 consecutive patients operated for CRC (42 stage I or II and 71 with stage III or IV) was retrospectively analyzed. The expression of MMR genes (MSH2, MLH1, MSH6 and PSM2) and co-stimulatory molecule CD80 was assessed by tissue microarray immunohistochemistry. In addition, tumor infiltrating mononuclear cells (TIMC) and T cell subpopulations (CD4, CD8, T-bet and FoxP-3) were quantified. The effect of specific siRNA (siMSH2, siMLH1, siMSH6 and siPSM2) transfection in HT29 on CD80 expression was quantified by flow cytometry. Non parametric statistics and survival analysis were used. Results: Patients with MMR-D showed a higher T-bet/CD4 ratio (p = 0.02), a higher rate of CD80 expression and CD8 lymphocyte infiltration compared to those with no MMR-D. Moreover, in the MMR-D group, the Treg marker FoxP-3 was not expressed (p = 0.05). MMR-D patients with stage I or II and T-bet expression had a significant better survival (p = 0.009). Silencing of MSH2, MLH1 and MSH6, but not PSM2, significantly increased the rate of CD80+ HT29 cells (p = 0.007, p = 0.023 and p = 0.015, respectively). Conclusions: CRC with MMR-D showed a higher CD80 expression, and CD8+ and Th1 T-cell infiltration. In vitro silencing of MSH2, MLH1 and MSH6 significantly increased CD80+ cell rate. These results suggest an enhanced immune surveillance mechanism in presence of MMR-D

From Photovoltaic to Agri-Natural-Voltaic (ANaV)

Italy is the geographic area with the highest world concentration of cultural sites, landscapes with a high esthetic value, and biodiversity. Therefore, any modification in the territory is to be performed by highly considering these cultural, landscape, and natural values. Also, Italy has a high human pressure on agricultural areas, especially in flatlands, that generally have a high agronomic value. As a consequence, the planning of photovoltaic installations in agricultural areas must meet at least five basic criteria: to cause as little use as possible to the agricultural soil, to maintain agricultural activities, to strengthen or introduce natural habitats, to properly mitigate the landscape impact, and to be located as far as possible from residential areas. This chapter presents the technological innovation with a high environmental value that characterizes the photovoltaic system, called Agro-Natural-Voltaic (AnaV), also using methodological and planning schemes together with landscape simulations. Moreover, the essay gives a description of the study on the environmental impact (for the administrative procedure of the Environmental Impact Assessment), laid down for the emblematic case study

Indicador composto estadual de inovação (ICEI): uma metodologia para avaliação de sistemas regionais de inovação

The methodological systematization of data collection, compilation and aggregation of Science, Technology and Innovation Indicators has proved to be an important component in the formulation and evaluation of public policies.  Thus, the aim of this article is to present a methodology for the construction of the State Composite Innovation Indicator that allows evaluating the innovative performance of regional innovation systems. The procedures used were: research by bibliographic materials, adaptation of the methodology proposed by the European Innovation Scoreboard and calculation of the databases available in the Brazilian statistical system. The methodology of the State Composite Innovation Indicator revealed strengths and weaknesses in the different dimensions of Brazilian regional innovation systems. Among them, in São Paulo, Rio Grande do Sul, Paraná and Rio de Janeiro, there were strength in human resources and research system, in the Amazon, on the other hand, there are weaknesses in these same dimensions and highlighting innovators and occupations.A sistematização metodológica de levantamento de dados, compilação e agregação de Indicadores de Ciência, Tecnologia e Inovação tem se mostrado um componente importante na formulação e avaliação de políticas públicas. Assim, o objetivo deste artigo é apresentar uma metodologia de construção do Indicador Composto Estadual de Inovação que permita avaliar o desempenho inovativo dos sistemas regionais de inovação. Os procedimentos utilizados foram: investigação por materiais bibliográficos, adaptação da metodologia proposta pelo European Innovation Scoreboard e apuração das bases de dados disponíveis no sistema estatístico brasileiro. A metodologia do Indicador Composto Estadual de Inovação revelou potencialidades e fragilidades nas distintas dimensões dos sistemas regionais de inovação brasileiros. Entre elas, em São Paulo, Rio Grande do Sul, Paraná e Rio de Janeiro, constataram-se forças em recursos humanos e sistema de pesquisa, no Amazonas, por outro lado, há fragilidades nessas mesmas dimensões e destaque em inovadores e ocupações

Pancreatic cancer spheres are more than just aggregates of stem marker-positive cells

Pancreatic cancer stem-like cells are described by membrane expression of CD24, CD44 and ESA (epithelial-specific antigen) and their capacity to grow as spheres in a serum-free medium containing well-defined growth factors. The capacity of a panel of four pancreatic cancer cell lines (PANC-1, CFPAC-1, PancTu-1 and PSN-1) to form spheres was tested. All cell lines with the exception of PancTu-1 developed spheres. Phenotypically, the sphere-growing cells showed an increased in vitro invasion capability. Both gene and protein expressions of markers of metastases [CXCR4 (CXC chemokine receptor 4), OPN (osteopontin) and CD44v6] and components of active hedgehog pathway signalling were assessed. Spheres clearly demonstrated increased expression of the above-mentioned markers when compared with their adherent counterpart. With the aim of identifying a minimum set of markers able to separate cells that have the capacity to form spheres from those incapable of forming spheres, a PCA (principal component analysis) of the multidimensional dataset was performed. Although PCA of the ‘accepted’ stemness genes was unable to separate sphere-forming from sphere-incapable cell lines, the addition of the ‘aggressiveness’ marker CD44v6 allowed a clear differentiation. Moreover, inoculation of the spheres and the adherent cells in vivo confirmed the superior aggressiveness (proliferation and metastasis) of the spheres over the adherent cells. In conclusion, the present study suggests that the sphere-growing cell population is not only composed of cells displaying classical stem membrane markers but also needs CD44v6-positive cells to successfully form spheres. Our results also emphasize the potential therapeutic importance of pathways such as CXCR4 and hedgehog for pancreatic cancer treatment