User-made immobilities: a transitions perspective

In this paper we aim to conceptualize the role of users in creating, expanding and stabilizing the automobility system. Drawing on transition studies we offer a typology of user roles including user-producers, user-legitimators, user-intermediaries, user-citizens and user-consumers, and explore it on the historical transition to the automobile regime in the USA. We find that users play an important role during the entire transition process, but some roles are more salient than others in particular phases. Another finding is that the success of the transition depends on the stabilization of the emerging regime that will trigger upscaling in terms of the numbers of adopters. The findings are used to reflect on potential crossovers between transitions and mobilities research

A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumours

To assess tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical activity of the dual epidermal growth factor receptor (EGFR) 1 and 2 (HER2) tyrosine kinase inhibitor BIBW 2992. An escalating schedule of once-daily (OD) BIBW 2992 for 14 days followed by 14 days off medication was explored. Thirty-eight patients were enrolled. Dose levels were 10, 20, 30, 45, 70, 85, and 100 mg. At 100 mg dose-limiting toxicity (DLT) (common toxicity criteria grade 3 skin rash and grade 3 diarrhoea despite treatment with loperamide) occurred in two patients. In the next-lower dose of 70 mg, DLT (grade 3 fatigue and ALAT elevation) occurred in one of six patients. An intermediate dose level of 85 mg was studied. Here DLT occurred in two patients (grade 3 diarrhoea despite treatment and grade 2 diarrhoea lasting more than 7 days despite treatment). An additional 12 patients were treated at 70 mg. BIBW 2992 PK after single and multiple doses revealed moderately fast absorption, and no deviation from dose proportionality. Pharmacodynamics analysis in skin biopsies did not show significant changes in EGFR-associated biomarkers. However, a significant inhibitory effect on the proliferation index of epidermal keratinocytes was observed. No partial or complete responses were observed, stable disease lasting more than four cycles was seen in seven patients. The recommended dose for studies with BIBW 2992 for 14 days followed by 14 days off medication is 70 mg OD

A Social Sciences and Humanities research agenda for transport and mobility in Europe: key themes and 100 research questions

Transport and mobility systems need to be transformed to meet climate change goals and reduce negative environmental and social effects. Despite EU policies having targeted such problems for more than three decades, transitions have been slow and geographically uneven. For effective change to happen, transport and mobility research needs fresh perspectives and better integration of knowledge from the Social Sciences and Humanities. Based on a Horizon Scanning approach, which allowed for a great deal of openness and variety in scholarly viewpoints, this paper presents a novel research agenda consisting of 8 themes and 100 research questions that may contribute to achieving environmentally sustainable mobility transitions within Europe. This research agenda highlights the need to not only support technological solutions for low-carbon mobility, but the importance of transformative policies that include new processes of knowledge production, civic participation and epistemic justice. We contend that the agenda points to the need for further research on the dynamics of science-society interactions

Behavior in behavioral strategy : capturing, measuring, analyzing

Measuring behavior requires research methods that can capture observed outcomes and expose underlying processes and mechanisms. In this chapter, we present a toolbox of instruments and techniques we designed experimental tasks to simulate decision environments and capture behavior. We deployed protocol analysis and text analysis to examine the underlying cognitive processes. In combination, these can simultaneously grasp antecedents, outcomes, processes, and mechanisms. We applied them to collect rich behavioral data on two key topics in strategic management: the exploration–exploitation trade-off and strategic risk-taking. This mix of methods is particularly useful in describing actual behavior as it is, not as it should be, replacing assumptions with data and offering a finer-grained perspective of strategic decision-making

The role of war in deep transitions: exploring mechanisms, imprints and rules in sociotechnical systems

This paper explores in what ways the two world wars influenced the development of sociotechnical systems underpinning the culmination of the first deep transition. The role of war is an underexplored aspect in both the Techno-Economic Paradigms (TEP) approach and the Multi-level perspective (MLP) which form the two key conceptual building blocks of the Deep Transitions (DT) framework. Thus, we develop a conceptual approach tailored to this particular topic which integrates accounts of total war and mechanisms of war from historical studies and imprinting from organisational studies with the DT framework’s attention towards rules and meta-rules. We explore in what ways the three sociotechnical systems of energy, food, and transport were affected by the emergence of new demand pressures and logistical challenges during conditions of total war; how war impacted the directionality of sociotechnical systems; the extent to which new national and international policy capacities emerged during wartime in the energy, food, and transport systems; and the extent to which these systems were influenced by cooperation and shared sacrifice under wartime conditions. We then explore what lasting changes were influenced by the two wars in the energy, food, and transport systems across the transatlantic zone. This paper seeks to open up a hitherto neglected area in analysis on sociotechnical transitions and we discuss the importance of further research that is attentive towards entanglements of warfare and the military particularly in the field of sustainability transitions

A Social Sciences and Humanities research agenda for transport and mobility in Europe: key themes and 100 research questions

Transport and mobility systems need to be transformed to meet climate change goals and reduce negative environmental and social effects. Despite EU policies having targeted such problems for more than three decades, transitions have been slow and geographically uneven. For effective change to happen, transport and mobility research needs fresh perspectives and better integration of knowledge from the Social Sciences and Humanities. Based on a Horizon Scanning approach, which allowed for a great deal of openness and variety in scholarly viewpoints, this paper presents a novel research agenda consisting of 8 themes and 100 research questions that may contribute to achieving environmentally sustainable mobility transitions within Europe. This research agenda highlights the need to not only support technological solutions for low-carbon mobility, but the importance of transformative policies that include new processes of knowledge production, civic participation and epistemic justice. We contend that the agenda points to the need for further research on the dynamics of science-society interactions

PolyQ Repeat Expansions in ATXN2 Associated with ALS Are CAA Interrupted Repeats

Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressive disease leading to paralysis and death. Recently, intermediate length polyglutamine (polyQ) repeats of 27–33 in ATAXIN-2 (ATXN2), encoding the ATXN2 protein, were found to increase risk for ALS. In ATXN2, polyQ expansions of ≥34, which are pure CAG repeat expansions, cause spinocerebellar ataxia type 2. However, similar length expansions that are interrupted with other codons, can present atypically with parkinsonism, suggesting that configuration of the repeat sequence plays an important role in disease manifestation in ATXN2 polyQ expansion diseases. Here we determined whether the expansions in ATXN2 associated with ALS were pure or interrupted CAG repeats, and defined single nucleotide polymorphisms (SNPs) rs695871 and rs695872 in exon 1 of the gene, to assess haplotype association. We found that the expanded repeat alleles of 40 ALS patients and 9 long-repeat length controls were all interrupted, bearing 1–3 CAA codons within the CAG repeat. 21/21 expanded ALS chromosomes with 3CAA interruptions arose from one haplotype (GT), while 18/19 expanded ALS chromosomes with <3CAA interruptions arose from a different haplotype (CC). Moreover, age of disease onset was significantly earlier in patients bearing 3 interruptions vs fewer, and was distinct between haplotypes. These results indicate that CAG repeat expansions in ATXN2 associated with ALS are uniformly interrupted repeats and that the nature of the repeat sequence and haplotype, as well as length of polyQ repeat, may play a role in the neurological effect conferred by expansions in ATXN2