Plasma MicroRNA Signature Validation for Early Detection of Colorectal Cancer

OBJECTIVES: Specific microRNA (miRNA) signatures in biological fluids can facilitate earlier detection of the tumors being then minimally invasive diagnostic biomarkers. Circulating miRNAs have also emerged as promising diagnostic biomarkers for colorectal cancer (CRC) screening. In this study, we investigated the performance of a specific signature of miRNA in plasma samples to design a robust predictive model that can distinguish healthy individuals from those with CRC or advanced adenomas (AA) diseases. METHODS: Case control study of 297 patients from 8 Spanish centers including 100 healthy individuals, 101 diagnosed with AA, and 96 CRC cases. Quantitative real-time reverse transcription was used to quantify a signature of miRNA (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) in plasma samples. Binary classifiers (Support Vector Machine [SVM] linear, SVM radial, and SVM polynomial) were built for the best predictive model. RESULTS: Area under receiving operating characteristic curve of 0.92 (95% confidence interval 0.871-0.962) was obtained retrieving a model with a sensitivity of 0.85 and specificity of 0.90, positive predictive value of 0.94, and negative predictive value of 0.76 when advanced neoplasms (CRC and AA) were compared with healthy individuals. CONCLUSIONS: We identified and validated a signature of 6 miRNAs (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) as predictors that can differentiate significantly patients with CRC and AA from those who are healthy. However, large-scale validation studies in asymptomatic screening participants should be conducted

BRIVA-LIFE–A multicenter retrospective study of the long-term use of brivaracetam in clinical practice

Objectives: Evaluate long-term effectiveness and tolerability of brivaracetam in clinical practice in patients with focal epilepsy. Materials and Methods: This was a multicenter retrospective study. Patients aged =16 years were started on brivaracetam from November 2016 to June 2017 and followed over 1 year. Data were obtained from medical records at 3, 6 and 12 months after treatment initiation for evaluation of safety- and seizure-related outcomes. Results: A total of 575 patients were included in analyses; most had been treated with =4 lifetime antiepileptic drugs. Target dosage was achieved by 30.6% of patients on the first day. Analysis of primary variables at 12 months revealed that mean reduction in seizure frequency was 36.0%, 39.7% of patients were =50% responders and 17.5% were seizure-free. Seizure-freedom was achieved by 37.5% of patients aged =65 years. Incidence of adverse events (AEs) and psychiatric AEs (PAEs) was 39.8% and 14.3%, respectively, and discontinuation due to these was 8.9% and 3.7%, respectively. Somnolence, irritability, and dizziness were the most frequently reported AEs. At baseline, 228 (39.7%) patients were being treated with levetiracetam; most switched to brivaracetam (dose ratio 1:10-15). Among those who switched because of PAEs (n = 53), 9 (17%) reported PAEs on brivaracetam, and 3 (5.7%) discontinued because of PAEs. Tolerability was not highly affected among patients with learning disability or psychiatric comorbidity. Conclusions: In a large population of patients with predominantly drug-resistant epilepsy, brivaracetam was effective and well-tolerated; no unexpected AEs occurred over 1 year, and the incidence of PAEs was lower compared with levetiracetam

Model-free classification of X-ray scattering signals applied to image segmentation

In most cases, the analysis of small-angle and wide-angle X-ray scattering (SAXS and WAXS, respectively) requires a theoretical model to describe the sample’s scattering, complicating the interpretation of the scattering resulting from complex heterogeneous samples. This is the reason why, in general, the analysis of a large number of scattering patterns, such as are generated by time- resolved and scanning methods, remains challenging. Here, a model-free classification method to separate SAXS/WAXS signals on the basis of their inflection points is introduced and demonstrated. This article focuses on the segmentation of scanning SAXS/WAXS maps for which each pixel corresponds to an azimuthally integrated scattering curve. In such a way, the sample composition distribution can be segmented through signal classification without applying a model or previous sample knowledge. Dimensionality reduction and clustering algorithms are employed to classify SAXS/WAXS signals according to their similarity. The number of clusters, i.e. the main sample regions detected by SAXS/WAXS signal similarity, is automatically estimated. From each cluster, a main representative SAXS/WAXS signal is extracted to uncover the spatial distribution of the mixtures of phases that form the sample. As examples of applications, a mudrock sample and two breast tissue lesions are segmented

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study

<p>Abstract</p> <p>Background</p> <p>A frequent manifestation of advanced NSCLC is malnutrition, even though there are many studies which relate it with a poor survival, its relation with toxicity has not yet been consistently reported. The aim of this study was to associate malnutrition and albumin serum levels with the occurrence of chemotherapy-induced toxicity in cisplatin plus paclitaxel chemotherapy-treated NSCLC.</p> <p>Methods</p> <p>We prospectively evaluated 100 stage IV NSCLC patients treated with paclitaxel (175 mg/m²) and cisplatin (80 mg/m²). Malnutrition was assessed using SGA prior treatment. Neutrophil Lymphocyte Ratio (NLR) and the Platelet Lymphocyte Ratio (PLR) were used to determine the presence of systemic inflammatory response (SIR) and were related to the development of toxicity. Toxicity was graded according to NCI CTCAE version 3.0 after two chemotherapy cycles.</p> <p>Results</p> <p>Median age was 58 ± 10 years, 51% of patients were malnourished, 50% had albumin ≤3.0 mg/mL. NLR ≥ 5 was associated with basal hypoalbuminemia (mean ranks, 55.7 vs. 39 p = 0.006), ECOG = 2 (47.2 vs. 55.4 p = 0.026) and PLR ≥ 150 were significantly related with a basal body mass index ≤20 (56.6 vs. 43.5; p = 0.02) and hypoalbuminemia (58.9 vs. 41.3; p = 0.02). Main toxicities observed after 2 cycles of chemotherapy were alopecia (84%), nausea (49%), neuropathy (46%), anemia (33%), lymphopenia (31%), and leukopenia (30%). Patients malnourished and with hypoalbuminemia developed more chemotherapy-induced toxicity overall when compared with those without malnutrition (31 vs 22; <it>p </it>= 0.02) and normal albumin (mean ranks, 62 vs 43; <it>p </it>= 0.002), respectively. Hypoalbuminemia was associated with anemia (56 vs 47; <it>p </it>= 0.05), fatigue (58 vs 46; <it>p </it>= 0.01), and appetite loss (57.1 vs 46.7; <it>p </it>= 0.004) compared with normal albumin. PLR ≥ 150 was related with the development of toxicity grade III/IV (59.27 vs. 47.03 p = 0.008) and anemia (37.9 vs 53.8 p = 0.004).</p> <p>Conclusion</p> <p>SIR parameters were associated with malnutrition, weight loss and hypoalbuminemia. Chemotherapy-induced toxicity in NSCLC patients treated with paclitaxel and cisplatin was associated with malnutrition and hypoalbuminemia. Early nutritional assessment and support might confer beneficial effects.</p

Global patterns and drivers of ecosystem functioning in rivers and riparian zones

River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.peerReviewe

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Calibration of the CMS Drift Tube Chambers and Measurement of the Drift Velocity with Cosmic Rays

Peer reviewe