Disseminated disease is present in ≈50% of colorectal cancer patients upon diagnosis, being responsible for most of cancer deaths. Addition of biological drugs, as Bevacizumab, to chemotherapy, has increased progression free survival and overall survival of metastatic colorectal cancer (mCRC) patients. However, these benefits have been only reported in a small proportion of patients. To date, there are not biomarkers that could explain the heterogeneity of this disease and would help in treatment selection. Recent findings demonstrated that microRNAs (miRNAs) play an important role in cancer and they can be encapsulated with high stability into extracellular vesicles (EVs) that are released in biological fluids. EVs can act as cell-to-cell communicators, transferring genetic information, such as miRNAs. In this context, we aimed to investigate serum EV associated miRNAs (EV-miRNAs) as novel non-invasive biomarkers for the diagnosis and prognosis of Bevacizumab-treated mCRC patients. We observed that baseline miRNA-21 and 92a outperformed carcinoembryonic antigen levels in the diagnosis of our 44 mCRC patients, compared to 17 healthy volunteers. In addition, patients who died presented higher levels of miRNA-92a and 222 at 24 weeks. However, in the multivariate Cox analysis, higher levels of miRNA-222 at 24 weeks were associated with lower overall survival. Altogether, these data indicate that EV-miRNAs have a strong potential as liquid biopsy biomarkers for the identification and prognosis of mCRC. Colorectal cancer (CRC) is the second most common cancer in women and the third most in men worldwide. Moreover, it accounts for 8.9% of all tumour-related mortality and is the second most common cause of cancer death 1. Disseminated disease is present upon diagnosis in 50% of the patients [lymph nodes (35%) and distant organs (22%)] and half of the patients diagnosed as localized tumours will eventually develop it 2. In recent years, the application of new targeted therapies, including anti-angiogenic drugs, has contributed to largely increase the overall survival (OS) of metastatic colorectal cancer mCRC patients, reporting median survivals of ≈30 months 3. Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF) has demonstrated benefits in progression-free survival (PFS) and OS in combination with chemotherapy 4,5 .

In this paper we present the first results of a study of BAL QSOs (at low and high redshift), based on very deep Gemini GMOS integral field spectroscopy. In particular, the results obtained for the nearest BAL IR–QSO Mrk 231 are presented. For the nuclear region of Mrk 231, the QSO and host galaxy components were modelled, using a new technique of decoupling 3D spectra. From this study, the following main results were found: (i) in the pure host galaxy spectrum an extreme nuclear starburst component was clearly observed, as a very strong increase in the flux, at the blue wavelengths; (ii) the BAL system I is observed in the spectrum of the host galaxy; (iii) in the clean/pure QSO emission spectrum, only broad lines were detected. 3D GMOS individual spectra (specially in the near‐infrared Ca ii triplet) and maps confirm the presence of an extreme and young nuclear starburst (8 < age < 15 Myr), which was detected in a ring or toroid with a radius r= 0.3 arcsec ∼ 200 pc, around the core of the nucleus. The extreme continuum blue component was detected only to the south of the core of the nucleus. This area is coincident with the region where we previously suggested that the galactic wind is cleaning the nuclear dust. Very deep 3D spectra and maps clearly show that the BAL systems I and II – in the strong ‘absorption lines’ Na iDλ5889–95 and Ca ii Kλ3933 – are extended (reaching ∼1.4–1.6 arcsec ∼ 1.2–1.3 kpc, from the nucleus) and clearly elongated at the position angle (PA) close to the radio jet PA, which suggest that the BAL systems I and II are ‘both’ associated with the radio jet. The physical properties of the four expanding nuclear bubbles were analysed, using the GMOS 3D spectra and maps. In particular, we found strong multiple LINER/OF emission‐line systems and Wolf–Rayet features in the main knots of the more external super bubble S1 (r= 3.0 kpc). The kinematics of these knots – and the internal bubbles – suggest that they are associated with an area of rupture of the shell S1 (at the south‐west). In addition, in the more internal superbubble S4 and close to the core of the nucleus (for r < 0.7 arcsec ∼ 0.6 kpc), two similar narrow emission‐line systems were detected, with strong [S ii] and [O i] emission and ΔV∼−200 km s−1. These results suggest that an important part of the nuclear NLR is generated by the OF process and the associated low‐velocity ionizing shocks. Finally, the nature of the composite BAL systems and very extended OF process – of 50 kpc – in Mrk 231 (and similar QSOs) are discussed. In addition, the ‘composite hyperwind scenario’ (already proposed for BALs) is suggested for the origin of giant Lyα blobs. The importance of study the end phases of Mrk 231, and similar evolving elliptical galaxies and QSOs (i.e. galaxy remnants) is discussed.

The analysis of burned human remains has been of great interest among forensic anthropologists largely due to the difficulty that their recovery, classification, reconstruction, and identification present. The main purpose of this analysis is to present histological methodology for the interpretation of bones altered by thermal processes. We include analyses of the microscopic changes among bones exposed to different temperatures, with the goal of establishing categories of histological morphology in relation to fire temperature. Samples of bone (ilium) were exposed systematically to controlled temperatures. Analysis of the resulting histological changes has allowed the formation of a clear four-stage classification of the alterations observed. This classification should prove useful in assessing bone changes in relation to temperature of exposure, particularly in cases where this temperature was previously not known.

No abstract