Systematic review and metaanalysis of genetic association studies of urinary symptoms and prolapse in women

Peer reviewe

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

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

Statistica

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

We (will) bank

Scommettereste mai che, in questo periodo di crisi del settore bancario, c’è qualcuno che festeggia un successo? Webank, la banca online del Gruppo Bipiemme, quest’anno compie dieci anni. E in questo libro Andrea Cardamone racconta la sua avventura alla guida della banca online pioniere dell’internet banking in Italia. Tra i fattori vincenti una visione del futuro lungimirante, la convergenza di scelte strategiche e tattiche in un mercato che cambia rapidamente, una naturale predisposizione alla relazione con il cliente e una condivisione senza compromessi delle logiche e del linguaggio del web. Dopo l’introduzione di Carlo Massarini, un vero e proprio excursus su internet e gli internauti dal 1999 a oggi, i primi capitoli raccontano la storia dell’online banking in Italia, le sfide e le linee di evoluzione di Webank alla luce dei cambiamenti emersi – anche – dalla recente crisi finanziaria, i tratti distintivi del marketing delle banche online e la sfida alle nuove modalità di comunicazione del web 2.0. La seconda parte del libro presenta il progetto di revisione linguistica dei principali materiali di comunicazione tra banca e clienti, dalle email automatiche, al sito web, ai documenti cartacei: un caso di studio emblematico sul tema della trasparenza bancaria e un’esperienza che fa di Webank un innovatore nel campo delle scelte linguistiche del settore

Sfide e linee guida per la crescita internazionale delle imprese familiari

I processi d’internazionalizzazione non sono indipendenti dall’assetto proprietario delle imprese, ed è possibile individuare uno specifico approccio alla crescita internazionale delle imprese a controllo familiare

Developing a Bayesian adaptive design for a phase I clinical trial: a case study for a novel HIV treatment

The design of phase I studies is often challenging, because of limited evidence to inform study protocols. Adaptive designs are now well established in cancer but much less so in other clinical areas. A phase I study to assess the safety, pharmacokinetic profile and antiretroviral efficacy of C34-PEG4-Chol, a novel peptide fusion inhibitor for the treatment of HIV infection, has been set up with Medical Research Council funding. During the study workup, Bayesian adaptive designs based on the continual reassessment method were compared with a more standard rule-based design, with the aim of choosing a design that would maximise the scientific information gained from the study. The process of specifying and evaluating the design options was time consuming and required the active involvement of all members of the trial's protocol development team. However, the effort was worthwhile as the originally proposed rule-based design has been replaced by a more efficient Bayesian adaptive design. While the outcome to be modelled, design details and evaluation criteria are trial specific, the principles behind their selection are general. This case study illustrates the steps required to establish a design in a novel context

Coadministration of Glucagon-Like Peptide-1 During Glucagon Infusion in Humans Results in Increased Energy Expenditure and Amelioration of Hyperglycemia

Glucagon and glucagon-like peptide (GLP)-1 are the primary products of proglucagon processing from the pancreas and gut, respectively. Giving dual agonists with glucagon and GLP-1 activity to diabetic, obese mice causes enhanced weight loss and improves glucose tolerance by reduction of food intake and by increase in energy expenditure (EE). We aimed to observe the effect of a combination of glucagon and GLP-1 on resting EE and glycemia in healthy human volunteers. In a randomized, double-blinded crossover study, 10 overweight or obese volunteers without diabetes received placebo infusion, GLP-1 alone, glucagon alone, and GLP-1 plus glucagon simultaneously. Resting EE—measured using indirect calorimetry—was not affected by GLP-1 infusion but rose significantly with glucagon alone and to a similar degree with glucagon and GLP-1 together. Glucagon infusion was accompanied by a rise in plasma glucose levels, but addition of GLP-1 to glucagon rapidly reduced this excursion, due to a synergistic insulinotropic effect. The data indicate that drugs with glucagon and GLP-1 agonist activity may represent a useful treatment for type 2 diabetes and obesity. Long-term studies are required to demonstrate that this combination will reduce weight and improve glycemia in patients