Significant changes to the referendum process are required to make direct democracy deliberative in practice

Despite their surface similarity, deliberative democracy and direct democracy often pull in different directions. In this context, Lawrence LeDuc asks how the conduct of referendums can be made more deliberative. He finds that the process is currently inhibited by the intrusion of politics, the absence of clarity, the amount and quality of information, and the degree of participation and engagement of citizens in the process

When who and how matter: explaining the success of referendums in Europe

This article aims to identify the institutional factors that make a referendum successful. This comparative analysis seeks to explain the success of top-down referendums organized in Europe between 2001 and 2013. It argues and tests for the main effect of three institutional factors (popularity of the initiator, size of parliamentary majority, and political cues during referendum campaigns) and controls for the type of referendum and voter turnout. The analysis uses data collected from referendums and electoral databases, public opinion surveys, and newspaper articles. Results show that referendums proposed by a large parliamentary majority or with clear messages from political parties during campaign are likely to be successful

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Seismic geomorphology of cretaceous megaslides offshore Namibia (Orange Basin):Insights into segmentation and degradation of gravity-driven linked systems

This study applies modern seismic geomorphology techniques to deep-water collapse features in the Orange Basin (Namibian margin, Southwest Africa) in order to provide unprecedented insights into the segmentation and degradation processes of gravity-driven linked systems. The seismic analysis was carried out using a high-quality, depth-migrated 3D volume that images the Upper Cretaceous post-rift succession of the basin, where two buried collapse features with strongly contrasting seismic expression are observed. The lower Megaslide Complex is a typical margin-scale, extensional-contractional gravity-driven linked system that deformed at least 2 km of post-rift section. The complex is laterally segmented into scoop-shaped megaslides up to 20 km wide that extend downdip for distances in excess of 30 km. The megaslides comprise extensional headwall fault systems with associated 3D rollover structures and thrust imbricates at their toes. Lateral segmentation occurs along sidewall fault systems which, in the proximal part of the megaslides, exhibit oblique extensional motion and define horst structures up to 6 km wide between individual megaslides. In the toe areas, reverse slip along these same sidewall faults, creates lateral ramps with hanging wall thrust-related folds up to 2 km wide. Headwall rollover anticlines, sidewall horsts and ramp anticlines may represent novel traps for hydrocarbon exploration on the Namibian margin.The Megaslide Complex is unconformably overlain by few hundreds of metres of highly contorted strata which define an upper Slump Complex. Combined seismic attributes and detailed seismic facies analysis allowed mapping of headscarps, thrust imbrications and longitudinal shear zones within the Slump Complex that indicate a dominantly downslope movement of a number of coalesced collapse systems. Spatial and stratal relationships between these shallow failures and the underlying megaslides suggest that the Slump Complex was likely triggered by the development of topography created by the activation of the main structural elements of the lower Megaslide Complex. This study reveals that gravity-driven linked systems undergo lateral segmentation during their evolution, and that their upper section can become unstable, favouring the initiation of a number of shallow failures that produce widespread degradation of the underlying megaslide structures. Gravity-driven linked systems along other margins are likely to share similar processes of segmentation and degradation, implying that the megaslide-related, hydrocarbon trapping structures discovered in the Namibian margin may be common elsewhere, making megaslides an attractive element of deep-water exploration along other gravitationally unstable margins

Phase II study of preoperative radiation plus concurrent daily tegafur-uracil (UFT) with leucovorin for locally advanced rectal cancer

<p>Abstract</p> <p>Background</p> <p>Considerable variation in intravenous 5-fluorouracil (5-FU) metabolism can occur due to the wide range of dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can affect both tolerability and efficacy. The oral fluoropyrimidine tegafur-uracil (UFT) is an effective, well-tolerated and convenient alternative to intravenous 5-FU. We undertook this study in patients with locally advanced rectal cancer to evaluate the efficacy and tolerability of UFT with leucovorin (LV) and preoperative radiotherapy and to evaluate the utility and limitations of multicenter staging using pre- and post-chemoradiotherapy ultrasound. We also performed a validated pretherapy assessment of DPD activity and assessed its potential influence on the tolerability of UFT treatment.</p> <p>Methods</p> <p>This phase II study assessed preoperative UFT with LV and radiotherapy in 85 patients with locally advanced T3 rectal cancer. Patients with potentially resectable tumors received UFT (300 mg/m/²/day), LV (75 mg/day), and pelvic radiotherapy (1.8 Gy/day, 45 Gy total) 5 days/week for 5 weeks then surgery 4-6 weeks later. The primary endpoints included tumor downstaging and the pathologic complete response (pCR) rate.</p> <p>Results</p> <p>Most adverse events were mild to moderate in nature. Preoperative grade 3/4 adverse events included diarrhea (n = 18, 21%) and nausea/vomiting (n = 5, 6%). Two patients heterozygous for dihydropyrimidine dehydrogenase gene (<it>DPYD</it>) experienced early grade 4 neutropenia (variant IVS14+1G > A) and diarrhea (variant 2846A > T). Pretreatment ultrasound TNM staging was compared with postchemoradiotherapy pathology TN staging and a significant shift towards earlier TNM stages was observed (p < 0.001). The overall downstaging rate was 42% for primary tumors and 44% for lymph nodes. The pCR rate was 8%. The sensitivity and specificity of ultrasound for staging was poor. Anal sphincter function was preserved in 55 patients (65%). Overall and recurrence-free survival at 3 years was 86.1% and 66.7%, respectively. Adjuvant chemotherapy was administered to 36 node-positive patients (mean duration 118 days).</p> <p>Conclusion</p> <p>Preoperative chemoradiotherapy using UFT with LV plus radiotherapy was well tolerated and effective and represents a convenient alternative to 5-FU-based chemoradiotherapy for the treatment of resectable rectal cancer. Pretreatment detection of DPD deficiency should be performed to avoid severe adverse events.</p

Mitogenomic phylogenetic analyses of the Delphinidae with an emphasis on the Globicephalinae

BACKGROUND: Previous DNA-based phylogenetic studies of the Delphinidae family suggest it has undergone rapid diversification, as characterised by unresolved and poorly supported taxonomic relationships (polytomies) for some of the species within this group. Using an increased amount of sequence data we test between alternative hypotheses of soft polytomies caused by rapid speciation, slow evolutionary rate and/or insufficient sequence data, and hard polytomies caused by simultaneous speciation within this family. Combining the mitogenome sequences of five new and 12 previously published species within the Delphinidae, we used Bayesian and maximum-likelihood methods to estimate the phylogeny from partitioned and unpartitioned mitogenome sequences. Further ad hoc tests were then conducted to estimate the support for alternative topologies. RESULTS: We found high support for all the relationships within our reconstructed phylogenies, and topologies were consistent between the Bayesian and maximum-likelihood trees inferred from partitioned and unpartitioned data. Resolved relationships included the placement of the killer whale (Orcinus orca) as sister taxon to the rest of the Globicephalinae subfamily, placement of the Risso's dolphin (Grampus griseus) within the Globicephalinae subfamily, removal of the white-beaked dolphin (Lagenorhynchus albirostris) from the Delphininae subfamily and the placement of the rough-toothed dolphin (Steno bredanensis) as sister taxon to the rest of the Delphininae subfamily rather than within the Globicephalinae subfamily. The additional testing of alternative topologies allowed us to reject all other putative relationships, with the exception that we were unable to reject the hypothesis that the relationship between L. albirostris and the Globicephalinae and Delphininae subfamilies was polytomic. CONCLUSION: Despite their rapid diversification, the increased sequence data yielded by mitogenomes enables the resolution of a strongly supported, bifurcating phylogeny, and a chronology of the divergences within the Delphinidae family. This highlights the benefits and potential application of large mitogenome datasets to resolve long-standing phylogenetic uncertainties