Online analysis of H2S and SO2 via advanced mid-Infrared gas sensors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Surrogate endpoints for prostate cancer-specific mortality after radiotherapy and androgen suppression therapy in men with localised or locally advanced prostate cancer: an analysis of two randomised trials

Background Androgen suppression therapy and radiotherapy are used to treat locally advanced prostate cancer. 3 years of androgen suppression confers a small survival benefit compared with 6 months of therapy in this setting, but is associated with more toxic effects. Early identification of men in whom radiotherapy and 6 months of androgen suppression is insufficient for cure is important. Thus, we assessed whether prostate-specific antigen (PSA) values can act as an early surrogate for prostate cancer-specific mortality (PCSM). Methods We systematically reviewed randomised controlled trials that showed improved overall and prostate cancer-specific survival with radiotherapy and 6 months of androgen suppression compared with radio therapy alone and measured lowest PSA concentrations (PSA nadir) and those immediately after treatment (PSA end). We assessed a cohort of 734 men with localised or locally advanced prostate cancer from two eligible trials in the USA and Australasia that randomly allocated participants between Feb 2, 1996, and Dec 27, 2001. We used Prentice criteria to assess whether reported PSA nadir or PSA end concentrations of more than 0.5 ng/mL were surrogates for PCSM. Findings Men treated with radiotherapy and 6 months of androgen suppression in both trials were significantly less likely to have PSA end and PSA nadir values of more than 0.5 ng/mL than were those treated with radiotherapy alone (p<0.0001). Presence of candidate surrogates (ie, PSA end and PSA nadir values >0.5 ng/mL) alone and when assessed in conjunction with the randomised treatment group increased risk of PCSM in the US trial (PSA nadir p=0.0016; PSA end p=0.017) and Australasian trial (PSA nadir p<0.0001; PSA end p=0.0012). In both trials, the randomised treatment group was no longer associated with PCSM (p >= 0.20) when the candidate surrogates were included in the model. Therefore, both PSA metrics satisfied Prentice criteria for surrogacy. Interpretation After radiotherapy and 6 months of androgen suppression, men with PSA end values exceeding 0.5 ng/mL should be considered for long-term androgen suppression and those with localised or locally advanced prostate cancer with PSA nadir values exceeding 0.5 ng/mL should be considered for inclusion in randomised trials investigating the use of drugs that have extended survival in castration-resistant metastatic prostate cancer.

Analysis of preferences for freight transport using advanced choice models

Programa de doctorado: Perspectivas científicas sobre el turismo y la dirección de empresas turísticas

Advanced spectroscopic techniques and chemometric analysis for atmospheric organic aerosol characterization and source apportionment

Atmospheric aerosol particles directly impact air quality and participate in controlling the climate system. Organic Aerosol (OA) in general accounts for a large fraction (10–90%) of the global submicron (PM1) particulate mass. Chemometric methods for source identification are used in many disciplines, but methods relying on the analysis of NMR datasets are rarely used in atmospheric sciences. This thesis provides an original application of NMR-based chemometric methods to atmospheric OA source apportionment. The method was tested on chemical composition databases obtained from samples collected at different environments in Europe, hence exploring the impact of a great diversity of natural and anthropogenic sources. We focused on sources of water-soluble OA (WSOA), for which NMR analysis provides substantial advantages compared to alternative methods. Different factor analysis techniques are applied independently to NMR datasets from nine field campaigns of the project EUCAARI and allowed the identification of recurrent source contributions to WSOA in European background troposphere: 1) Marine SOA; 2) Aliphatic amines from ground sources (agricultural activities, etc.); 3) Biomass burning POA; 4) Biogenic SOA from terpene oxidation; 5) “Aged” SOAs, including humic-like substances (HULIS); 6) Other factors possibly including contributions from Primary Biological Aerosol Particles, and products of cooking activities. Biomass burning POA accounted for more than 50% of WSOC in winter months. Aged SOA associated with HULIS was predominant (> 75%) during the spring-summer, suggesting that secondary sources and transboundary transport become more important in spring and summer. Complex aerosol measurements carried out, involving several foreign research groups, provided the opportunity to compare source apportionment results obtained by NMR analysis with those provided by more widespread Aerodyne aerosol mass spectrometers (AMS) techniques that now provided categorization schemes of OA which are becoming a standard for atmospheric chemists. Results emerging from this thesis partly confirm AMS classification and partly challenge it.

Molecular subtype analysis determines the association of advanced breast cancer in Egypt with favorable biology

Background Prognostic markers and molecular breast cancer subtypes reflect underlying biological tumor behavior and are important for patient management. Compared to Western countries, women in North Africa are less likely to be prognosticated and treated based on well-characterized markers such as the estrogen receptor (ER), progesterone receptor (PR) and Her2. We conducted this study to determine the prevalence of breast cancer molecular subtypes in the North African country of Egypt as a measure of underlying biological characteristics driving tumor manifestations. Methods To determine molecular subtypes we characterized over 200 tumor specimens obtained from Egypt by performing ER, PR, Her2, CK5/6, EGFR and Ki67 immunohistochemistry. Results Our study demonstrated that the Luminal A subtype, associated with favorable prognosis, was found in nearly 45% of cases examined. However, the basal-like subtype, associated with poor prognosis, was found in 11% of cases. These findings are in sharp contrast to other parts of Africa in which the basal-like subtype is over-represented. Conclusions Egyptians appear to have favorable underlying biology, albeit having advanced disease at diagnosis. These data suggest that Egyptians would largely profit from early detection of their disease. Intervention at the public health level, including education on the benefits of early detection is necessary and would likely have tremendous impact on breast cancer outcome in Egypt.

Predictors of severe late radiotherapy-related toxicity after hyperfractionated radiotherapy with or without concomitant cisplatin in locally advanced head and neck cancer. Secondary retrospective analysis of a randomized phase III trial (SAKK 10/94)

This secondary analysis was performed to identify predictive factors for severe late radiotherapy (RT)-related toxicity after treatment with hyperfractionated RT +/- concomitant cisplatin in locally advanced head and neck cancer.

Japanese-US common-arm analysis of paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a model for assessing population-related pharmacogenomics

PURPOSE To explore whether population-related pharmacogenomics contribute to differences in patient outcomes between clinical trials performed in Japan and the United States, given similar study designs, eligibility criteria, staging, and treatment regimens. METHODS We prospectively designed and conducted three phase III trials (Four-Arm Cooperative Study, LC00-03, and S0003) in advanced-stage, non-small-cell lung cancer, each with a common arm of paclitaxel plus carboplatin. Genomic DNA was collected from patients in LC00-03 and S0003 who received paclitaxel (225 mg/m(2)) and carboplatin (area under the concentration-time curve, 6). Genotypic variants of CYP3A4, CYP3A5, CYP2C8, NR1I2-206, ABCB1, ERCC1, and ERCC2 were analyzed by pyrosequencing or by PCR restriction fragment length polymorphism. Results were assessed by Cox model for survival and by logistic regression for response and toxicity. Results Clinical results were similar in the two Japanese trials, and were significantly different from the US trial, for survival, neutropenia, febrile neutropenia, and anemia. There was a significant difference between Japanese and US patients in genotypic distribution for CYP3A4*1B (P = .01), CYP3A5*3C (P = .03), ERCC1 118 (P < .0001), ERCC2 K751Q (P < .001), and CYP2C8 R139K (P = .01). Genotypic associations were observed between CYP3A4*1B for progression-free survival (hazard ratio [HR], 0.36; 95% CI, 0.14 to 0.94; P = .04) and ERCC2 K751Q for response (HR, 0.33; 95% CI, 0.13 to 0.83; P = .02). For grade 4 neutropenia, the HR for ABCB1 3425C-->T was 1.84 (95% CI, 0.77 to 4.48; P = .19). CONCLUSION Differences in allelic distribution for genes involved in paclitaxel disposition or DNA repair were observed between Japanese and US patients. In an exploratory analysis, genotype-related associations with patient outcomes were observed for CYP3A4*1B and ERCC2 K751Q. This common-arm approach facilitates the prospective study of population-related pharmacogenomics in which ethnic differences in antineoplastic drug disposition are anticipated.

Effect of initial treatment strategy on survival of patients with advanced-stage Hodgkin's lymphoma: a systematic review and network meta-analysis

BACKGROUND Several treatment strategies are available for adults with advanced-stage Hodgkin's lymphoma, but studies assessing two alternative standards of care-increased dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated), and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-were not powered to test differences in overall survival. To guide treatment decisions in this population of patients, we did a systematic review and network meta-analysis to identify the best initial treatment strategy. METHODS We searched the Cochrane Library, Medline, and conference proceedings for randomised controlled trials published between January, 1980, and June, 2013, that assessed overall survival in patients with advanced-stage Hodgkin's lymphoma given BEACOPPbaseline, BEACOPPescalated, BEACOPP variants, ABVD, cyclophosphamide (mechlorethamine), vincristine, procarbazine, and prednisone (C[M]OPP), hybrid or alternating chemotherapy regimens with ABVD as the backbone (eg, COPP/ABVD, MOPP/ABVD), or doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone combined with radiation therapy (the Stanford V regimen). We assessed studies for eligibility, extracted data, and assessed their quality. We then pooled the data and used a Bayesian random-effects model to combine direct comparisons with indirect evidence. We also reconstructed individual patient survival data from published Kaplan-Meier curves and did standard random-effects Poisson regression. Results are reported relative to ABVD. The primary outcome was overall survival. FINDINGS We screened 2055 records and identified 75 papers covering 14 eligible trials that assessed 11 different regimens in 9993 patients, providing 59 651 patient-years of follow-up. 1189 patients died, and the median follow-up was 5·9 years (IQR 4·9-6·7). Included studies were of high methodological quality, and between-trial heterogeneity was negligible (τ(2)=0·01). Overall survival was highest in patients who received six cycles of BEACOPPescalated (HR 0·38, 95% credibility interval [CrI] 0·20-0·75). Compared with a 5 year survival of 88% for ABVD, the survival benefit for six cycles of BEACOPPescalated is 7% (95% CrI 3-10)-ie, a 5 year survival of 95%. Reconstructed individual survival data showed that, at 5 years, BEACOPPescalated has a 10% (95% CI 3-15) advantage over ABVD in overall survival. INTERPRETATION Six cycles of BEACOPPescalated significantly improves overall survival compared with ABVD and other regimens, and thus we recommend this treatment strategy as standard of care for patients with access to the appropriate supportive care.

A Global Trend towards Democratic Convergence? A Lijphartian Analysis of Advanced Democracies.

The article offers a systematic analysis of the comparative trajectory of international democratic change. In particular, it focuses on the resulting convergence or divergence of political systems, borrowing from the literatures on institutional change and policy convergence. To this end, political-institutional data in line with Arend Lijphart’s (1999, 2012) empirical theory of democracy for 24 developed democracies between 1945 and 2010 are analyzed. Heteroscedastic multilevel models allow for directly modeling the development of the variance of types of democracy over time, revealing information about convergence, and adding substantial explanations. The findings indicate that there has been a trend away from extreme types of democracy in single cases, but no unconditional trend of convergence can be observed. However, there are conditional processes of convergence. In particular, economic globalization and the domestic veto structure interactively influence democratic convergence.

Trends and outcomes in the use of surgery and radiation for the treatment of locally advanced esophageal cancer: a propensity score adjusted analysis of the surveillance, epidemiology, and end results registry from 1998 to 2008

We examined outcomes and trends in surgery and radiation use for patients with locally advanced esophageal cancer, for whom optimal treatment isn't clear. Trends in surgery and radiation for patients with T1-T3N1M0 squamous cell or adenocarcinoma of the mid or distal esophagus in the Surveillance, Epidemiology, and End Results database from 1998 to 2008 were analyzed using generalized linear models including year as predictor; Surveillance, Epidemiology, and End Results doesn't record chemotherapy data. Local treatment was unimodal if patients had only surgery or radiation and bimodal if they had both. Five-year cancer-specific survival (CSS) and overall survival (OS) were analyzed using propensity-score adjusted Cox proportional-hazard models. Overall 5-year survival for the 3295 patients identified (mean age 65.1 years, standard deviation 11.0) was 18.9% (95% confidence interval: 17.3-20.7). Local treatment was bimodal for 1274 (38.7%) and unimodal for 2021 (61.3%) patients; 1325 (40.2%) had radiation alone and 696 (21.1%) underwent only surgery. The use of bimodal therapy (32.8-42.5%, P = 0.01) and radiation alone (29.3-44.5%, P < 0.001) increased significantly from 1998 to 2008. Bimodal therapy predicted improved CSS (hazard ratios [HR]: 0.68, P < 0.001) and OS (HR: 0.58, P < 0.001) compared with unimodal therapy. For the first 7 months (before survival curve crossing), CSS after radiation therapy alone was similar to surgery alone (HR: 0.86, P = 0.12) while OS was worse for surgery only (HR: 0.70, P = 0.001). However, worse CSS (HR: 1.43, P < 0.001) and OS (HR: 1.46, P < 0.001) after that initial timeframe were found for radiation therapy only. The use of radiation to treat locally advanced mid and distal esophageal cancers increased from 1998 to 2008. Survival was best when both surgery and radiation were used.

How political economies affect immigrants' socio-economic incorporation. A comparative analysis of immigrants’ poverty risks across advanced industrialised countries

Immigration and the resulting increasing ethnic diversity have become an important characteristic of advanced industrialised countries. At the same time, the majority of the countries in question are confronted with structural transformation such as deindustrialisation and changes in family structures as well as economic downturn, which limit the capacities of nation-states in addressing rising inequality and supporting those individuals at the margins of the society. This paper addresses both issues, immigration and inequality, by focusing on immigrants’ socio-economic incorporation into the receiving societies of advanced industrialised countries. The aim of this paper is to explain cross-national variation in immigrants’ poverty risks. Drawing on the political economy as well as the migration literature, the paper develops a theoretical framework that considers how the impact of the national labour market and welfare system on immigrants’ poverty risks is moderated by the integration policies, which regulate immigrants’ access to the labour market and social programs (or immigrants’ economic and social rights). The empirical analysis draws on income surveys as well as a newly collected data set on economic and social rights of immigrants in 19 advanced industrialised countries, including European countries as well as Australia, and North America, for the year 2007. As the results from multilevel analysis show, integration policies concerning immigrants’ access to the labour market and social programs can partly explain cross-national variations in immigrants’ poverty risks. In line with the hypothesis, stricter labour market regulations such as minimum wage setting reduce immigrants’ poverty risks stronger in countries where they are granted easier access to the labour market. However, concerning the impact of more generous social programs the reductive poverty effect is stronger in countries with less inclusive access of immigrants to social programs. The paper concludes by discussing possible explanations for this puzzling finding.

Analysis of Chromatic Aberration Effects in Triple-Junction Solar Cells Using Advanced Distributed Models

The consideration of real operating conditions for the design and optimization of a multijunction solar cell receiver-concentrator assembly is indispensable. Such a requirement involves the need for suitable modeling and simulation tools in order to complement the experimental work and circumvent its well-known burdens and restrictions. Three-dimensional distributed models have been demonstrated in the past to be a powerful choice for the analysis of distributed phenomena in single- and dual-junction solar cells, as well as for the design of strategies to minimize the solar cell losses when operating under high concentrations. In this paper, we present the application of these models for the analysis of triple-junction solar cells under real operating conditions. The impact of different chromatic aberration profiles on the short-circuit current of triple-junction solar cells is analyzed in detail using the developed distributed model. Current spreading conditions the impact of a given chromatic aberration profile on the solar cell I-V curve. The focus is put on determining the role of current spreading in the connection between photocurrent profile, subcell voltage and current, and semiconductor layers sheet resistance.

Advanced methodologies for the dendrogeomorphic analysis of past floods and related risks

This communication presents an overview of their first results and innovate methodologies, focused in their possibilities and limitations for the reconstruction of recent floods and paleofloods over the World.