Predictive Factors for Second-Line Therapy in Metastatic Renal Cell Carcinoma: A Retrospective Analysis

Currently, about 50% of patients with metastatic renal cell carcinoma (mRCC) receive a second-line therapy. Therefore, the choice at each subsequent treatment line remains an important issue. In this retrospective study, we sought to identify pretreatment clinical parameters that could predict the likelihood of a patient receiving a second-line therapy. One hundred and sixty-one mRCC patients who received targeted therapy were evaluated. Descriptive statistics, Kaplan–Meier overall survival (OS), Cox regression, and binary logistic regression models were used for data analysis. Second-line therapy was given to 105 patients (65%). Patients with grade 1 tumor received second-line therapy more frequently than those with grade 2/3 tumors (P = 0.03). Only tumor grade was significantly different between patients receiving, or not receiving, second-line treatment. Median OS was significantly superior in patients receiving second-line therapy (32 versus 14 months; P = 0.007; hazard ratio [HR], 1.75; P = 0.008), patients with grade 1 tumors (130 versus 29 months in G2/3 tumors; HR, 3.85; P = 0.009), and in patients without early tumor progression (41 versus 11 months; HR, 5.04; 95% confidence interval [CI], 3.06–8.31; P < 0.001). In binary logistic regression, we identified early progression to be significantly associated with a higher probability of not receiving a second-line therapy (HR, 2.50; 95% CI, 1.01–6.21; P = 0.048). This study hypothesizes that pretreatment grade and early progression are predictive parameters for the selection of patients for second-line therapy

Parameters from site classification to harmonize MRI clinical studies: Application to a multi-site Parkinson's disease dataset

Multi-site MRI datasets are crucial for big data research. However, neuroimaging studies must face the batch effect. Here, we propose an approach that uses the predictive probabilities provided by Gaussian processes (GPs) to harmonize clinical-based studies. A multi-site dataset of 216 Parkinson's disease (PD) patients and 87 healthy subjects (HS) was used. We performed a site GP classification using MRI data. The outcomes estimated from this classification, redefined like Weighted HARMonization PArameters (WHARMPA), were used as regressors in two different clinical studies: A PD versus HS machine learning classification using GP, and a VBM comparison (FWE-p < .05, k = 100). Same studies were also conducted using conventional Boolean site covariates, and without information about site belonging. The results from site GP classification provided high scores, balanced accuracy (BAC) was 98.39% for grey matter images. PD versus HS classification performed better when the WHARMPA were used to harmonize (BAC = 78.60%; AUC = 0.90) than when using the Boolean site information (BAC = 56.31%; AUC = 0.71) and without it (BAC = 57.22%; AUC = 0.73). The VBM analysis harmonized using WHARMPA provided larger and more statistically robust clusters in regions previously reported in PD than when the Boolean site covariates or no corrections were added to the model. In conclusion, WHARMPA might encode global site-effects quantitatively and allow the harmonization of data. This method is user-friendly and provides a powerful solution, without complex implementations, to clean the analyses by removing variability associated with the differences between sites

Early and Middle Holocene Hunter-Gatherer Occupations in Western Amazonia: The Hidden Shell Middens

We report on previously unknown early archaeological sites in the Bolivian lowlands, demonstrating for the first time early and middle Holocene human presence in western Amazonia. Multidisciplinary research in forest islands situated in seasonally-inundated savannahs has revealed stratified shell middens produced by human foragers as early as 10,000 years ago, making them the oldest archaeological sites in the region. The absence of stone resources and partial burial by recent alluvial sediments has meant that these kinds of deposits have, until now, remained unidentified. We conducted core sampling, archaeological excavations and an interdisciplinary study of the stratigraphy and recovered materials from three shell midden mounds. Based on multiple lines of evidence, including radiocarbon dating, sedimentary proxies (elements, steroids and black carbon), micromorphology and faunal analysis, we demonstrate the anthropogenic origin and antiquity of these sites. In a tropical and geomorphologically active landscape often considered challenging both for early human occupation and for the preservation of hunter-gatherer sites, the newly discovered shell middens provide evidence for early to middle Holocene occupation and illustrate the potential for identifying and interpreting early open-air archaeological sites in western Amazonia. The existence of early hunter-gatherer sites in the Bolivian lowlands sheds new light on the region's past and offers a new context within which the late Holocene "Earthmovers" of the Llanos de Moxos could have emerged. © 2013 Lombardo et al

Caveolin 1 protein expression in renal cell carcinoma predicts survival

<p>Abstract</p> <p>Background</p> <p>Caveolae play a significant role in disease phenotypes such as cancer, diabetes, bladder dysfunction, and muscular dystrophy. The aim of this study was to elucidate the caveolin-1 <it>(</it>CAV1<it>) </it>protein expression in renal cell cancer (RCC) and to determine its potential prognostic relevance.</p> <p>Methods</p> <p>289 clear cell RCC tissue specimens were collected from patients undergoing surgery for renal tumors. Both cytoplasmic and membranous CAV1 expression were determined by immunohistochemistry and correlated with clinical variables. Survival analysis was carried out for 169 evaluable patients with a median follow up of 80.5 months (interquartile range (IQR), 24.5 - 131.7 months).</p> <p>Results</p> <p>A high CAV1 expression in the tumor cell cytoplasm was significantly associated with male sex (p = 0.04), a positive nodal status (p = 0.04), and poor tumor differentiation (p = 0.04). In contrast, a higher than average (i.e. > median) CAV1 expression in tumor cell membranes was only linked to male sex (p = 0.03). Kaplan-Meier analysis disclosed significant differences in 5-year overall (51.4 vs. 75.2%, p = 0.001) and tumor specific survival (55.3 vs. 80.1%, p = 0.001) for patients with higher and lower than average cytoplasmic CAV1 expression levels, respectively. Applying multivariable Cox regression analysis a high CAV1 protein expression level in the tumor cell cytoplasm could be identified as an independent poor prognostic marker of both overall (p = 0.02) and tumor specific survival (p = 0.03) in clear cell RCC patients.</p> <p>Conclusion</p> <p>Over expression of caveolin-1 in the tumour cell cytoplasm predicts a poor prognosis of patients with clear cell RCC. CAV1 is likely to be a useful prognostic marker and may play an important role in tumour progression. Therefore, our data encourage further investigations to enlighten the role of CAV1 and its function as diagnostic and prognostic marker in serum and/or urine of RCC patients.</p

Multiomics in the central Arctic Ocean for benchmarking biodiversity change

Multiomics approaches need to be applied in the central Arctic Ocean to benchmark biodiversity change and to identify novel species and their genes. As part of MOSAiC, EcoOmics will therefore be essential for conservation and sustainable bioprospecting in one of the least explored ecosystems on Earth

Comparison of Facetted and Blunt Lifting Bodies for Re-Entry Flight

The design of a re-entry vehicle strongly depends on the entry strategy of the projected mission. From the aerodynamic point of view, the layout of a hypersonic vehicle is a compromise between a vehicle being blunt enough to reduce the aerodynamic heating and sharp enough to obtain acceptable aerodynamic and propulsive efficiency. The selected flight configurations in this paper are wingless lifting bodies. Two different types of lifting bodies are compared: a sharp and a blunt body. The chosen blunt bicone is one of the ReFEx geometries, which was designed in the frame of the DLR vehicle concept study of ReFEx (Reusability Flight Experiment). The sharp configuration is one of the DLR SHEFEX (SHarp Edge Flight EXperiment) configurations, which is a facetted body with sharp leading edge. The focus of the present study is the discussion of advantages and drawbacks of both concepts with respect to structure and aerodynamics

Comparison of Faceted and Blunt Lifting Bodies for Reentry Flights

The design of a reentry vehicle strongly depends on the entry strategy of the projected mission. From the aerodynamic point of view, the layout of a hypersonic vehicle is a compromise between a vehicle being blunt enough to reduce the aerodynamic heating and sharp enough to obtain acceptable aerodynamic and propulsive efficiency. The selected flight configurations in this paper are wingless lifting bodies. Two different types of lifting bodies are compared: a sharp and a blunt body. The chosen blunt bicone is one of the Reusability Flight Experiment geometries, which were designed in the frame of the DLR, German Aerospace Center vehicle concept study of Reusability Flight Experiment. The sharp configuration is one of the DLR, German Aerospace Center Sharp Edge Flight Experiment configurations, which are a faceted body with sharp leading edge. The focus of the present study is the discussion of advantages and drawbacks of both concepts with respect to structure and aerodynamics

Age—an independent prognostic factor of clinical outcome in renal malignancies: results of a large study over two decades

Age has been linked to outcome in renal cancer patients, but mainly in North American cohorts. In this study, we hypothesized that age is correlated with metastasis and cancer-specific survival in a German cohort regardless of types of treatments. A total of 1,538 patients treated for renal malignancies between 1991 and 2010 were evaluated. Mean age and median age are 61.9 ± 11.6 and 62.6 years. Clinicopathologic [tumor type, size, grade, stage and treatment (surgery, chemotherapy, radiation, immunotherapy)] and outcome parameters (metastasis and survival) were examined for an association with age using logistic regression and Cox proportional hazard model, and Kaplan–Meier plots. Age was associated with stage, metastasis, treatment, cancer-specific and overall mortality (p 63 years were lower than those for patients ≤63 years (p 63 years of age had 29–35 % higher risk of metastasis and cancer-specific mortality than younger patients. Median metastasis-free and cancer-specific survival for patients >63 years of age (months: 84.4; 70.3) was ~50 % shorter than in patients ≤63 years (months: 151; 144.6).This large study shows that, despite advances in surgical and non-surgical treatment modalities over the two decades, age is an independent prognostic indicator of metastasis and cancer-specific mortality in renal cancer patients. Patients >63 years have ~30 % increased risk for metastasis and ~50 % shorter cancer-specific survival

The Shefex Flight Experiment - Pathfinder Experiment for a Sky Based Test Facility

On Thursday, October 27th, 2005 the SHarp Edge Flight EXperiment SHEFEX has been successfully launched at the Andoya Rocket Range in northern Norway. The project, being performed under responsibility of the German Aerospace Center (DLR) flew on top of a two-stage solid propellant sounding rocket. One purpose of the experiment is the investigation of possible new shapes for future launcher or re-entry vehicles applying a shape with facetted surfaces and sharp edges and to enable the time accurate investi-gation of the flow effects and their structural answer during the hypersonic flight from 90 km down to an altitude of 20 km. Additionally, the SHEFEX project is a starting point for a series of experiments which enable the acquisition of important knowledge in hypersonic free flight experimentation and which are an excellent test bed for new technological concepts. The present paper gives an overview about the philosophy and the layout of ex- periment and introduces preliminary outcomes of the post-flight analysis