Observational study of chronic myeloid leukemia Italian patients who discontinued tyrosine kinase inhibitors in clinical practice.

It is judged safe to discontinue treatment with tyrosine kinase inhibitors for chronic myeloid leukemia in experimental trials on treatment free remission. We collected a total of 293 Italian patients with chronic phase chronic myeloid leukemia who discontinued tyrosine kinase inhibitors in deep molecular response. 72% of patients were on treatment with imatinib, 28% with second generation tyrosine kinase inhibitors at the time of discontinuation. Median duration of treatment with the last tyrosine kinase inhibitor was 77 months (IQR 54;111), median duration of deep molecular response was 46 months (IQR 31;74). Duration of treatment with tyrosine kinase inhibitors and duration of deep molecular response were shorter with 2nd generation tyrosine kinase inhibitors than with imatinib (p<0.001). 88% of the Italian patients discontinued per clinical practice and reasons for stopping treatment were: toxicity for 20% of patients, pregnancy for 6% patients and shared decision between treating physician and patient for 62% of cases. After a median follow-up of 34 months (Min-Max 12-161) overall estimated treatment free remission was 62% (95% CI 56;68). At 12 months treatment free remission was 68% (95% CI 62;74) for imatinib, 73% (95% CI 64;83) for 2nd generation tyrosine kinase inhibitors. Overall median time to restart treatment was 6 months (IQR 4;11). No progressions occurred. Although our study has the limitation of a retrospective study, our experience within the Italian population confirms that discontinuation of imatinib and 2nd generation tyrosine kinase inhibitors is feasible and safe in the clinical practic

Low‐carbon transition risks for finance

The transition to a low‐carbon economy will entail a large‐scale structural change. Some industries will have to expand their relative economic weight, while other industries, especially those directly linked to fossil fuel production and consumption, will have to decline. Such a systemic shift may have major repercussions on the stability of financial systems, via abrupt asset revaluations, defaults on debt, and the creation of bubbles in rising industries. Studies on previous industrial transitions have shed light on the financial transition risks originating from rapidly rising “sunrise” industries. In contrast, a similar conceptual understanding of risks from declining “sunset” industries is currently lacking. We substantiate this claim with a critical review of the conceptual and historical literature, which also shows that most literature either examines structural change in the real economy, or risks to financial stability, but rarely both together. We contribute to filling this research gap by developing a consistent theoretical framework of the drivers, transmission channels, and impacts of the phase‐out of carbon‐intensive industries on the financial system and on the feedback from the financial system into the rest of the economy. We also review the state of play of policy aiming to protect the financial system from transition risks and spell out research implications

The thesis of "doux commerce" and the social licence to operate framework

The "doux commerce" thesis holds that commerce acts as a civilising force, contributing to the advancement and well-being of societies by inculcating certain core moral values in individuals (such as honesty, tolerance and fair-dealing). This idea has a venerable history. However, I suggest that it faces a particular challenge in the current era in light of examples of systemic misbehaviour by global companies. This paper explores the nature of this challenge, taking the events around the financial crisis of 2007-8 as a case study, and suggests that if we are to preserve the idea that commerce contributes to the common good then greater mechanisms of constraint on the worst excesses of business behaviour will be needed. In particular, I argue that we must recognise the need for all firms to have a social purpose and suggest that the ‘social licence to operate’ framework, familiar from the mining and extraction sectors, could be used to provide crucial leverage on the behaviour of multinational firms

Hydrogen-induced cracking of 500 HBW steels studied using a novel tuning-fork test with integrated loadcell system

Abstract Hydrogen embrittlement is a well-known problem with high-strength steels. An important aspect of hydrogen embrittlement research is the effect of the prior austenite grain (PAG) structure on hydrogen-induced fracture. The microstructural anisotropy of PAG structure depends on the steel manufacturing process. In this study, 500 HBW martensitic steels with different PAG structures are investigated with a novel tuning-fork test that utilizes an integrated loadcell system. The loadcell clamping system is used during hydrogen charging, allowing tracking of the applied force throughout the tests, which enables detection of separate phases of cracking and time-to-fracture. The elongated PAG morphology produces different results depending on the crack path direction in relation to the rolling direction, whereas the equiaxed PAG morphology does not manifest an orientation dependence. Depending on the PAG shape, also the fracture morphology differs. Time-to-fracture results show that elongated grain morphologies with transgranular quasi-cleavage crack propagation are more beneficial against hydrogen-induced fracture than equiaxed grain structure with intergranular crack propagation. These results demonstrate that the shape of the PAG structure plays an important role in the crack propagation mechanism and that it is important to consider the possible direction of hydrogen-induced cracks in the final structural applications