Efficacy end points were not significantly different between experimental and reference arms, although toxicities showed differences. These findings suggest that chemotherapy in NSCLC has reached a therapeutic plateau.

In response to various types of human disturbance, most Italian rivers have experienced considerable channel adjustment during the last centuries and in particular in the last decades. This paper reviews all existing published studies and available data, and aims to reconstruct a general outline of the main channel adjustments that have occurred in Italian rivers during the past 100 years.Two main types of channel adjustment have been recognized: (a) incision, which is commonly on the order of 3 -4 m, but in some cases is even more than 10 m; (b) narrowing, with channel width reduction up to 50% or more. In some reaches, these adjustments have led to changes in channel pattern in particular from braided to wandering.Such channel adjustments are due to several types of human intervention, particularly sediment extraction, dams and channelization. A strong temporal relationship (specifically, short reaction times) between human disturbance and channel adjustment can be inferred, but trends of adjustment are available for only a few rivers (e.g. the Po, the Arno and the Piave Rivers). These trends show that incision and/or narrowing are more intense immediately after the disturbance and then slow and become asymptotic; the same trends also suggest that larger rivers could have longer relaxation times.The results of this study are synthesised in a general classification scheme that summarises the main styles of adjustment observed in Italian rivers. According to the scheme, braided rivers adjust through prevalent narrowing with varying rates of incision, whereas single-thread rivers adjust mainly through a more pronounced incision accompanied by various amounts of narrowing. The scheme, representing initial and final (present) morphologies and not including intermediate stages of channel adjustment, will need to be tested on the basis of more detailed data to have a wider application both to the Italian context and to fluvial systems elsewhere, affected by similar types of human disturbance causing a reduction of sediment supply. D

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A new index has been developed for the hydromorphological assessment of Italian rivers. The method was designed to comply with the EU Water Framework Directive requirements, but its use can be extended to other applications in river management. The evaluation of stream morphological quality is preceded by a phase of river segmentation, consisting of an initial division of the network into river reaches with homogeneous morphological characteristics. The evaluation procedure consists of a set of 28 indicators, which were defined to assess longitudinal and lateral continuity, channel pattern, cross section configuration, bed structure and substrate, and vegetation in the riparian corridor. These characteristics are analyzed in terms of geomorphological functionality, artificiality, and channel adjustments. Indicators, classes, and the scoring system were defined based on expert judgement. The scoring system leads to the definition of the Morphological Quality Index (MQI). Application of the method to 102 river reaches covering a wide range of physical conditions and human pressures of Italian streams enabled the testing of the overall methodology and the refinement of the indicators and scores. Limitations, strengths, and the applicability of the method are also discussed in the paper.

Contact CEH NORA team at noraceh@ceh.ac.ukThe NERC and CEH trademarks and logos ('the Trademarks') are registered trademarks of NERC in the UK and other countries, and may not be used without the prior written consent of the Trademark owner. 1The following paper is the final version prior to publication on 22 September 2015. are proposed, the way in which indicators could contribute to classification is discussed. All of the methods described in Table 1 consider a hierarchy of spatial units, but the degree to which they develop the other aspects of the conceptual approach proposed by Frissell et al.(1986) varies widely.2. Many of the frameworks focus entirely on hydromorphological processes and forms that are either directly measured or inferred. This is because interactions between processes and forms control the dynamic morphology or behaviour of rivers and their mosaics of habitats.Hydromorphological processes drive longitudinal and lateral connectivity within river networks and corridors, the assemblage and turnover of physical habitats, and the sedimentary and vegetation structures associated with those habitats.3. Some frameworks are conceptual, providing a way of thinking about or structuring analyses of river systems, and interpreting their processes, morphology and function (e.g. Frissell et al., 1986;Habersack, 2000;Fausch et al., 2002;Thorp et al., 2006;Beechie et al., 2010;McCluney et al., 2014). Some frameworks are more quantitative, generating one or more indices or classifications of spatial units that support assessment of river systems (e.g. Rosgen, 1994;González del Tánago and García de Jalón, 2004;Merovich et al., 2013;Rinaldi et al., 2013Rinaldi et al., , 2015a MacDonald, 2002;Brierley and Fryirs, 2005;Beechie et al., 2010; Rinaldi et al., 2013a Rinaldi et al., , 2015.In some cases, theoretical or historical analyses or consideration of specific future scenarios are used to develop space-time understanding that can support management decisionmaking (e.g. Buffington, 1997, 1998;Montgomery and MacDonald, 2002;Benda et al., 2004;Brierley and Fryirs, 2005;McCluney et al., 2014 , 1997, 1998Montgomery and MacDonald, 2002;Benda et al., 2004;Brierley and Fryirs, 2005;Merovich et al., 2013;Rinaldi et al., 2013Rinaldi et al., , 2015a. Furthermore, some of the frameworks include indicators of human pressures and their impacts (e.g. Merovich et al., 2013;McCluney et al., 2014;Rinaldi et al., 2013Rinaldi et al., , 2015a.6. Finally, although most frameworks could be described as incorporating processes to some degree, some methods are particularly process-based, even when processes are inferred from forms and associations rather than being quantified by direct measurements.Frameworks that consider temporal dynamics and trajectories of historical change (see point 4, above) are particularly effective in developing understanding of processes and the impacts of changed processes cascading through time and across spatial scales.Although the list of frameworks presented in Table 1 is far from comprehensive, ...