Single tube liquid biopsy for advanced non-small cell lung cancer

The need for a liquid biopsy in non-small cell lung cancer (NSCLC) patients is rapidly increasing. We studied the relation between overall survival (OS) and the presence of four cancer biomarkers from a single blood draw in advanced NSCLC patients: EpCAM(high) circulating tumor cells (CTC), EpCAM(low) CTC, tumor-derived extracellular vesicles (tdEV) and cell-free circulating tumor DNA (ctDNA). EpCAM(high) CTC were detected with CellSearch, tdEV in the CellSearch images and EpCAM(low) CTC with filtration after CellSearch. ctDNA was isolated from plasma and mutations present in the primary tumor were tracked with deep sequencing methods. In 97 patients, 21% had >= 2 EpCAM(high) CTC, 15% had >= 2 EpCAM(low) CTC, 27% had >= 18 tdEV and 19% had ctDNA with >= 10% mutant allele frequency. Either one of these four biomarkers could be detected in 45% of the patients and all biomarkers were present in 2%. In 11 out of 16 patients (69%) mutations were detected in the ctDNA. Two or more unfavorable biomarkers were associated with poor OS. The presence of EpCAM(high) CTC and elevated levels of tdEV and ctDNA was associated with a poor OS; however, the presence of EpCAM(low) CTC was not. This single tube approach enables simultaneous analysis of multiple biomarkers to explore their potential as a liquid biopsy

New measures to evaluate forecast accuracy

reservedIl confronto tra previsione ottenuta e dati effettivamente osservati avviene tramite l’utilizzo di diverse misure di accuratezza. Data la moltitudine di indici proposti, risulta opportuno valutare quale di essi sia il più idoneo a valutare correttamente i diversi metodi previsionali. L'elaborato propone un'analisi degli indici di valutazione di accuratezza dei modelli previsionali, esaminandone pregi e difetti, con un focus particolare su MASE, l'R-MAPE e l'AvgRelMAE

The method of constant stimuli with three rating categories and the use of Rasch models

Logistic Models support an alternative general solution to compute the point ofsubjective equality (Vidotto et al., I modelli simple logistic e rating scale nella determinazionedel punto di eguaglianza soggettivo: una nuova prospettiva per il metodo degli stimolicostanti, 1996) when the Method of Constant Stimuli is used (Bock and Jones, The Measurementand Prediction of Judgment and Choice, 1968). The Extended Logistic Models (Andrich,Appl. Psychol. Meas. II:581\u2013594, 1978) offer the theoretical frame to compute individual andgeneral thresholds when the method of constant stimuli is applied using a forced choice withmore than two alternatives. As an example of the advantages of the application of this procedure,we show a data-set derived from an experiment on rhythm perception (Maestrini, Lapercezione del cambiamento nei ritmi uditivi, 2003), where two groups of experimental andna\uefve subjects were asked to judge whether the listened rhythm was constant, accelerated ordecelerated. We have computed individual and general thresholds differentiating constancyfrom both acceleration and deceleration for all the different experimental conditions. Themain advantage of this solution, compared to traditional psychophysical techniques, is notonly related to better estimates of the individual point of subjective equality. The improvementcan be summarized in the available fit tests to verify the agreement between the modelboth for stimuli and subjects

Reducing Elevated Gravitational-Force Events through visual feedback: a simulator study

Road traffic accidents represent one of the leading causes of death across all age groups globally. Most of these accidents can be directly attributed to drivers\u2019 failure to select the correct driving speed. Thus, actions aimed to mitigate inappropriate driving performance, including speeding, are needed. Here, we used a dynamic driving simulator to investigate the effects of different real-time coaching programs on driving performance, specifically on the occurrence of Elevated Gravitational-Force Events (EGFEs). Forty-three drivers underwent a two-day evaluation. On the first day, participants \u2013after an initial screening and depending on their driving style\u2013 were divided into two groups: defensive vs. aggressive drivers. On the second day, they received a different type of real time visual feedback based on their driving performance. For each of the two driving style groups, half of the drivers received contingent positive feedback (when smooth driving events occurred), the other half received contingent negative feedback (when harsh driving events occurred). Thus, there were four groups based on driving style and feedback. Overall, results showed that among aggressive drivers contingent feedback \u2013independently from its type\u2013 reduces the occurrence of EGFEs. Potential applications of the proposed methodology include its use for Pay-how-you-drive programs aimed to improve driver speed control

Detection and Prognostic Relevance of Circulating and Disseminated Tumour Cell in Dogs with Metastatic Mammary Carcinoma: A Pilot Study

In human breast cancer, both circulating tumour cells (CTCs) in peripheral blood and disseminated tumour cells (DTCs) in the bone marrow are predictive of short survival and may be used as liquid biopsy to guide therapy. Herein we investigate, for the first time, the feasibility to quantify CTCs and DTCs in canine metastatic mammary carcinoma (MMC) with the automated CellSearch platform, which identifies tumour cells by immune-magnetic enrichment and fluorescent labelling. Using this approach before start of treatment, we could detect at least 1 CTC per 7.5 mL of peripheral blood in 12 out of 27 evaluable samples (44.4%) and at least 1 DTC per 1 mL of bone marrow in 11 out of 14 evaluable samples (78.6%). Conversely, we did not find any CTCs in the healthy, negative control dogs (n = 5) that we analysed in parallel. Interestingly, the levels of CTCs/DTCs and the prevalence of positive dogs closely resemble results obtained by CellSearch assay in metastatic breast cancer patients at diagnosis. Moreover, in the canine cohort, the presence of CTCs was significantly associated with poor outcome. These observations identify the first actionable marker in veterinarian oncology to guide treatment of canine MMC. Furthermore, our findings have important implications for human research, since it reinforce the value of canine MMC as model useful to speed up pharmacological studies with primary endpoint of overall survival, given the reduced life-span of the canine species

In vivo MRI measurement of microstructural constraints for direct drug delivery within the brain

Brain tissue microstructure may influence the efficient delivery of therapeutics within the brain. Diffusion Tensor Imaging (DTI) enables the depiction of tissue properties in vivo, and thus is potentially relevant for planning convection-enhanced delivery (CED) within the brain. We report on the quantitative assessment of the distribution of a Gadolinium solution infused by CED within the brain of a live ovine model. Infusate distributions were measured at multiple timepoints and compared to microstructural properties as depicted by DTI, thus demonstrating the impact of tissue features and catheter positioning on drug distribution in vivo