71 research outputs found

    Non-small cell lung cancer testing on reference specimens: an italian multicenter experience

    Get PDF
    Introduction: Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples. Methods: Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated. Results: Overall, a median DNA concentration of 3.3 ng/μL (range 0.1–10.0 ng/μL) and 13.4 ng/μL (range 2.0–45.8 ng/μL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/μL (range 0.2–11.9 ng/μL) and 9.3 ng/μL (range 0.5–18.0 ng/μL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation. Conclusions: Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice

    Croatia at the International Exhibition of Children\u27s Drawings in Beijing

    Get PDF
    Context Although family studies have shown that male lower urinary tract symptoms (LUTS) are highly heritable, no systematic review exists of genetic polymorphisms tested for association with LUTS. Objective To systematically review and meta-analyze studies assessing candidate polymorphisms/genes tested for an association with LUTS, and to assess the strength, consistency, and potential for bias among pooled associations. Evidence acquisition A systematic search of the PubMed and HuGE databases as well as abstracts of major urologic meetings was performed through to January 2013. Case-control studies reporting genetic associations in men with LUTS were included. Reviewers independently and in duplicate screened titles, abstracts, and full texts to determine eligibility, abstracted data, and assessed the credibility of pooled associations according to the interim Venice criteria. Authors were contacted for clarifications if needed. Meta-analyses were performed for variants assessed in more than two studies. Evidence synthesis We identified 74 eligible studies containing data on 70 different genes. A total of 35 meta-analyses were performed with statistical significance in five (ACE, ELAC2, GSTM1, TERT, and VDR). The heterogeneity was high in three of these meta-analyses. The rs731236 variant of the vitamin D receptor had a protective effect for LUTS (odds ratio: 0.64; 95% confidence interval, 0.49–0.83) with moderate heterogeneity (I2 = 27.2%). No evidence for publication bias was identified. Limitations include wide-ranging phenotype definitions for LUTS and limited power in most meta-analyses to detect smaller effect sizes. Conclusions Few putative genetic risk variants have been reliably replicated across populations. We found consistent evidence of a reduced risk of LUTS associated with the common rs731236 variant of the vitamin D receptor gene in our meta-analyses. Patient summary Combining the results from all previous studies of genetic variants that may cause urinary symptoms in men, we found significant variants in five genes. Only one, a variant of the vitamin D receptor, was consistently protective across different populations

    Development of fundamental understanding of the cure kinetics of benzoxazine epoxy blends

    Get PDF
    This study attempts to bridge the gap between the current fundamental understanding of benzoxazines on the monomer level and their macro scale thermo-mechanical properties. Bisphenol-A based benzoxazine (Bz) was blended with di- and tri-functional epoxies to reduce viscosity for processing, and their resulting thermal and mechanical properties were characterized. Additionally, the formation of inter-molecular and intra-molecular hydrogen bonds was investigated within a Bz-epoxy two component system. Activation energy, heat of reaction, degradation temperature, hydrogen bonding characterization and thermo-mechanical characterization were studied using a differential scanning calorimeter, dynamic mechanical analyzer, thermogravimetric analysis, Fourier transform infrared spectroscopy and quasistatic tensile testing. Preliminary results show a synergistic increase in Tg of the blends, for both di- and tri-funcitonal epoxy blends. Surprisingly, while the two components exhibit Tg’s of ~ 150-170 oC, the blended systems consistently exhibited a Tg in the range of 210-250 oC. This work aims to expand upon thermal and mechanical characterization data generated by our collaborator Ehsan Barjasteh for the benzoxazine – di-functional epoxy system, as well as explore a new benzoxazine – tri-functional epoxy-based system. Our underlying motivations in this study are to identify the origins of the synergistic increase in Tg upon blending through various thermo-mechanical characterization methods and in-situ FT-IR analysis of cure kinetics, as well as identifying the compositions and functionality which exhibit the most desirable combination of thermal and mechanical properties.M.S

    Statistica

    Full text link
    Gli argomenti trattati sono: Dati statistici, grafici, distribuzioni di frequenza; Indici di posizione e variabilità: media, mediana, moda; varianza e deviazione standard; Teoria della probabilità e analisi combinatoria: distribuzione normale, ipergeometrica, di Poisson, log-normale; Statistica inferenziale e Test di ipotesi: campioni e parametri campionari, distribuzioni t di Student e chi-quadrato; Statistica bivariata: tabelle a doppia entrata, frequenze condizionate, indipendenza e dipendenza statistica; Correlazione semplice, multipla e parziale: coefficienti di correlazione, rette e piani di regressione; Analisi delle serie temporali: medie mobili, stima del trend, coefficiente di autocorrelazione; Tecniche avanzate

    Quiste dermoide

    Full text link
    corecore