Environmental Monitoring of Water Quality as a Planning and Management Tool: A Case Study of the Rodrigo de Freitas Lagoon, Rio de Janeiro, Brazil

The Rodrigo de Freitas Lagoon is an urban water body, representing one of the most popular spots for the local community. It underwent serious environmental degradation, at first through its water mirror reduction and more recently through sewer inflows. Concurrently, the difficulty in renewing the water combined with adverse climatic conditions has repeatedly led to an alarming fish mortality rate. The monitoring of its water quality has been carried out as a management and planning tool that lead to the improvement of the environmental conditions. This study seeks to assess monitoring results by correlating the factors that might be the cause of a failure to comply with environmental regulations. Although it is evident that particular places in the Lagoon might be more often affected by illegal sewer discharges, no evidence could be found of any variations between the six sampling points. However, the rise in the levels of Escherichia coli, nitrogen and phosphorus, and the general temperature conditions, pH, and salinity of the water shows that the most significant alterations occurred in spring 2018.The complexity of the period of phytoplankton growth followed by the fish mortality from anoxia underlines the need for monitoring as a tool for a better understanding of the alterations, providing guidance with regard to the planning and management of the ecosystem

ANÁLISES DE RISCO E CONFIABILIDADE APLICADAS À GESTÃO DE ESTAÇÕES DE TRATAMENTO DE EFLUENTES INDUSTRIAIS (ETEIs): UMA REVISÃO CRÍTICA

As Estações de Tratamento de Efluentes Industriais (ETEIs), desde a etapa de projeto, devem obdecer a critérios de desempenho médio semelhantes àqueles utilizados para projeto de unidades de produção industrial. Deste modo, é fundamental que as indústrias reconheçam as unidades de tratamento de efluentes como plantas industriais e estabeleçam para essas, sistemas de gestão ambiental efetivos, providos de controles que garantam atendimento à legislação ambiental

Mass hierarchy, 2-3 mixing and CP-phase with Huge Atmospheric Neutrino Detectors

We explore the physics potential of multi-megaton scale ice or water Cherenkov detectors with low ($\sim 1$ GeV) threshold. Using some proposed characteristics of the PINGU detector setup we compute the distributions of events versus neutrino energy $E_\nu$ and zenith angle $\theta_z$, and study their dependence on yet unknown neutrino parameters. The $(E_\nu - \theta_z)$ regions are identified where the distributions have the highest sensitivity to the neutrino mass hierarchy, to the deviation of the 2-3 mixing from the maximal one and to the CP-phase. We evaluate significance of the measurements of the neutrino parameters and explore dependence of this significance on the accuracy of reconstruction of the neutrino energy and direction. The effect of degeneracy of the parameters on the sensitivities is also discussed. We estimate the characteristics of future detectors (energy and angle resolution, volume, etc.) required for establishing the neutrino mass hierarchy with high confidence level. We find that the hierarchy can be identified at $3\sigma$ -- $10\sigma$ level (depending on the reconstruction accuracies) after 5 years of PINGU operation.Comment: 39 pages, 21 figures. Description of Fig.3 correcte

What do we have to know about PD-L1 expression in prostate cancer? A systematic literature review. part 4: Experimental treatments in pre-clinical studies (cell lines and mouse models)

In prostate cancer (PC), the PD-1/PD-L1 axis regulates various signaling pathways and it is influenced by extracellular factors. Pre-clinical experimental studies investigating the effects of various treatments (alone or combined) may discover how to overcome the immunotherapyresistance in PC-patients. We performed a systematic literature review (PRISMA guidelines) to delineate the landscape of pre-clinical studies (including cell lines and mouse models) that tested treatments with effects on PD-L1 signaling in PC. NF-kB, MEK, JAK, or STAT inhibitors on human/mouse, primary/metastatic PC-cell lines variably down-modulated PD-L1-expression, reducing chemoresistance and tumor cell migration. If PC-cells were co-cultured with NK, CD8+ Tcells or CAR-T cells, the immune cell cytotoxicity increased when PD-L1 was downregulated (opposite effects for PD-L1 upregulation). In mouse models, radiotherapy, CDK4/6-inhibitors, and RB deletion induced PD-L1-upregulation, causing PC-immune-evasion. Epigenetic drugs may reduce PD-L1 expression. In some PC experimental models, blocking only the PD-1/PD-L1 pathway had limited efficacy in reducing the tumor growth. Anti-tumor effects could be increased by combining the PD-1/PD-L1 blockade with other approaches (inhibitors of tyrosine kinase, PI3K/mTOR or JAK/STAT3 pathways, p300/CBP; anti-RANKL and/or anti-CTLA-4 antibodies; cytokines; nitroxoline; DNA/cell vaccines; radiotherapy/Radium-223)

What do we have to know about PD-L1 expression in prostate cancer? A systematic literature review. Part 3: PD-L1, intracellular signaling pathways and tumor microenvironment

The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients’ serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells

What do we have to know about pd-l1 expression in prostate cancer? A systematic literature review. part 1: Focus on immunohistochemical results with discussion of pre-analytical and interpretation variables

Immunotherapy targeting the PD-1–PD-L1 axis yielded good results in treating different immunologically ‘‘hot’’ tumors. A phase II study revealed good therapeutic activity of pembroli-zumab in selected prostatic carcinoma (PC)-patients. We performed a systematic literature review (PRISMA guidelines), which analyzes the immunohistochemical expression of PD-L1 in human PC samples and highlights the pre-analytical and interpretation variables. Interestingly, 29% acinar PCs, 7% ductal PCs, and 46% neuroendocrine carcinomas/tumors were PD-L1+ on immunohisto-chemistry. Different scoring methods or cut-off criteria were applied on variable specimen-types, evaluating tumors showing different clinic-pathologic features. The positivity rate of different PD-L1 antibody clones in tumor cells ranged from 3% (SP142) to 50% (ABM4E54), excluding the single case tested for RM-320. The most tested clone was E1L3N, followed by 22C3 (most used for pem-brolizumab eligibility), SP263, SP142, and 28-8, which gave the positivity rates of 35%, 11–41% (de-pending on different scoring systems), 6%, 3%, and 15%, respectively. Other clones were tested in <200 cases. The PD-L1 positivity rate was usually higher in tumors than benign tissues. It was higher in non-tissue microarray specimens (41–50% vs. 15%), as PC cells frequently showed heterogenous or focal PD-L1-staining. PD-L1 was expressed by immune or stromal cells in 12% and 69% cases, respectively. Tumor heterogeneity, inter-institutional preanalytics, and inter-observer interpretation variability may account for result biases

Factors influencing the normalization of CD4+ T-cell count, percentage and CD4+/CD8+ T-cell ratio in HIV-infected patients on long-term suppressive antiretroviral therapy

AbstractWe evaluated factors associated with normalization of the absolute CD4+ T-cell counts, per cent CD4+ T cells and CD4+/CD8+ T-cell ratio. A multicentre observational study was carried out in patients with sustained HIV-RNA <50 copies/mL. Outcomes were: CD4-count >500/mm3 and multiple T-cell marker recovery (MTMR), defined as CD4+ T cells >500/mm3 plus %CD4 T cells >29% plus CD4+/CD8+ T-cell ratio >1. Kaplan-Meier survival analysis and Cox regression analyses to predict odds for achieving outcomes were performed. Three hundred and fifty-two patients were included and followed-up for a median of 4.1 (IQR 2.1–5.9) years, 270 (76.7%) achieving a CD4+ T-cell count >500 cells/mm3 and 197 (56%) achieving MTMR. Using three separate Cox models for both outcomes we demonstrated that independent predictors were: both absolute CD4+ and CD8+ T-cell counts, %CD4+ T cells, a higher CD4+/CD8+ T-cell ratio, and age. A likelihood-ratio test showed significant improvements in fitness for the prediction of either CD4+ >500/mm3 or MTMR by multivariable analysis when the other immune markers at baseline, besides the absolute CD4+ count alone, were considered. In addition to baseline absolute CD4+ T-cell counts, pretreatment %CD4+ T cells and the CD4+/CD8+ T-cell ratio influence recovery of T-cell markers, and their consideration should influence the decision to start antiretroviral therapy. However, owing to the small sample size, further studies are needed to confirm these results in relation to clinical endpoints

Predicting Breast Cancer Response to Neoadjuvant Chemotherapy Using Pretreatment Diffuse Optical Spectroscopic-Texture Analysis

Purpose: Diffuse optical spectroscopy (DOS) has been demonstrated capable of monitoring response to neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC) patients. In this study, we evaluate texture features of pre-treatment DOS functional maps for predicting LABC response to NAC. Methods: LABC patients (n = 37) underwent DOS-breast imaging before starting neoadjuvant chemotherapy. Breast-tissue parametric maps were constructed and texture analyses were performed based on grey level co-occurrence matrices (GLCM) for feature extraction. Ground-truth labels as responders (R) or non-responders (NR) were assigned to patients based on Miller-Payne pathological response criteria. The capability of DOS-textural features computed on volumetric tumour data before the start of treatment (i.e. “pre-treatment”) to predict patient responses to NAC was evaluated using a leave-one-out validation scheme at subject level. Data were analysed using a logistic regression, naïve Bayes, and k-nearest neighbour (k-NN) classifiers. Results: Data indicated that textural characteristics of pre-treatment DOS parametric maps can differentiate between treatment response outcomes. The HbO2-homogeneity resulted in the highest accuracy amongst univariate parameters in predicting response to chemotherapy: sensitivity (%Sn) and specificity (%Sp) were 86.5 and 89.0%, respectively and accuracy was 87.8%. The highest predictors using multivariate (binary) combination features were the Hb-Contrast + HbO2-Homogeneity which resulted in a %Sn/%Sp = 78.0/81.0% and an accuracy of 79.5%. Conclusions: This study demonstrated that pre-treatment tumour DOS-texture features can predict breast cancer response to NAC and potentially guide treatments

The Impact of International Organizations on the Environment: An Empirical Analysis

When analyzing the impact of international organizations on the environment, two main issues arise. First, we have to quantify the participation of the organizations on countries they deal with. Second, the environmental impact of this involvement has to be measured. This paper attempts to do this. We employ panel data to empirically analyze whether and to what extent the presence of IMF, World Bank, regional Multilateral Development Banks, WTO and Global Environmental Facilities has an impact on environmental governance and outcomes. Our results for a large number of countries and years show that the international organizations affect the environment directly via their impact on CO2 emissions. Projects financed by World Bank, ADB, UNDP, and membership in the WTO increase emissions, while IADB projects reduce emissions. EBRD and UNEP do not significantly affect CO2 emissions, while the AfDB increases emissions after 1985 only. Taking the indirect impact through trade liberalization into account, however, the WTO reduces emissions, while the IADB increases emissions. There is some evidence that the international organizations investigated here also influence SO2 emissions, water pollution, and round wood production; environmental governance is not affected