Drilling their own graves:How the European oil and gas supermajors avoid sustainability tensions through mythmaking

This study explores how paradoxical tensions between economic growth and environmental protection are avoided through organizational mythmaking. By examining the European oil and gas supermajors’ ‘‘CEOspeak’’ about climate change, we show how mythmaking facilitates the disregarding, diverting, and/or displacing of sustainability tensions. In doing so, our findings further illustrate how certain defensive responses are employed: (1) regression, or retreating to the comforts of past familiarities, (2) fantasy, or escaping the harsh reality that fossil fuels and climate change are indeed irreconcilable, and (3) projecting, or shifting blame to external actors for failing to address climate change. By highlighting the discursive effects of enacting these responses, we illustrate how the European oil and gas supermajors self-determine their inability to substantively address the complexities of climate change. We thus argue that defensive responses are not merely a form of mismanagement as the paradox and corporate sustainability literature commonly suggests, but a strategic resource that poses serious ethical concerns given the imminent danger of issues such as climate change

Impact of smoking status on the relative efficacy of the EGFR TKI/angiogenesis inhibitor combination therapy in advanced NSCLC-a systematic review and meta-analysis.

BACKGROUND The ETOP 10-16 BOOSTER trial failed to demonstrate a progression-free survival (PFS) benefit for adding bevacizumab to osimertinib in second line. An exploratory subgroup analysis, however, suggested a PFS benefit of the combination in patients with a smoking history and prompted us to do this study. METHODS A systematic review and meta-analysis to evaluate the differential effect of smoking status on the benefit of adding an angiogenesis inhibitor to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor therapy was carried out. All relevant randomized controlled trials appearing in main oncology congresses or in PubMed as of 1 November 2021 were used according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Primarily PFS according to smoking status, and secondarily overall survival (OS) were of interest. Pooled and interaction hazard ratios (HRs) were estimated by fixed or random effects models, depending on the detected degree of heterogeneity. Bias was assessed using the revised Cochrane tool for randomized controlled trials (RoB 2). RESULTS Information by smoking was available for 1291 patients for PFS (seven studies) and 678 patients for OS (four studies). The risk of bias was low for all studies. Combination treatment significantly prolonged PFS for smokers [n = 502, HR = 0.55, 95% confidence interval (CI): 0.44-0.69] but not for nonsmokers (n = 789, HR = 0.92, 95% CI: 0.66-1.27; treatment-by-smoking interaction P = 0.02). Similarly, a significant OS benefit was found for smokers (n = 271, HR = 0.66, 95% CI: 0.47-0.93) but not for nonsmokers (n = 407, HR = 1.07, 95% CI: 0.82-1.42; treatment-by-smoking interaction P = 0.03). CONCLUSION In advanced EGFR-non-small-cell lung cancer patients, the addition of an angiogenesis inhibitor to EGFR-tyrosine kinase inhibitor therapy provides a statistically significant PFS and OS benefit in smokers, but not in non-smokers. The biological basis for this observation should be pursued and could determine whether this might be due to a specific co-mutational pattern produced by tobacco exposure

A randomized open-label phase III trial evaluating the addition of denosumab to standard first-line treatment in advanced NSCLC : the European Thoracic Oncology Platform (ETOP) and European Organisation for Research and Treatment of Cancer (EORTC) SPLENDOUR trial

Introduction Receptor activator of NF-kB ligand stimulates NF-kB–dependent cell signaling and acts as the primary signal for bone resorption. Retrospective analysis of a large trial comparing denosumab versus zoledronic acid in bone metastatic solid tumors suggested significant overall survival (OS) advantage for patients with lung cancer with denosumab (p = 0.01). The randomized open-label phase III SPLENDOUR trial was designed to evaluate whether the addition of denosumab to standard first-line platinum-based doublet chemotherapy improved OS in advanced NSCLC. Methods Patients with stage IV NSCLC were randomized in a 1:1 ratio to either chemotherapy with or without denosumab (120 mg every 3–4 wks), stratified by the presence of bone metastases (at diagnosis), Eastern Cooperative Oncology Group performance status, histology, and region. To detect an OS increase from 9 to 11.25 months (hazard ratio [HR] = 0.80), 847 OS events were required. The trial closed prematurely owing to decreasing accrual rate. Results A total of 514 patients were randomized, with 509 receiving one or more doses of the assigned treatment (chemotherapy: 252, chemotherapy-denosumab: 257). The median age was 66.1 years, 71% were men, and 59% were former smokers. Bone metastases were identified in 275 patients (53%). Median OS (95% confidence interval [CI]) was 8.7 (7.6–11.0) months in the control arm versus 8.2 (7.5–10.4) months in the chemotherapy-denosumab arm (HR = 0.96; 95% CI: 0.78–1.19; one-sided p = 0.36). For patients with bone metastasis, HR was 1.02 (95% CI: 0.77–1.35), whereas for those without, HR was 0.90 (95% CI: 0.66–1.23). Adverse events grade 3 or greater were observed in 40.9%, 5.2%, 8.7% versus 45.5%, 10.9%, 10.5% of patients. Conditional power for OS benefit was less than or equal to 10%. Conclusions Denosumab was well-tolerated without unexpected safety concerns. There was no OS improvement for denosumab when added to chemotherapy in the intention-to-treat population and the subgroups with and without bone metastases. Our data do not provide evidence of a clinical benefit for denosumab in patients with NSCLC without bone metastases

Incidência e fatores de risco de lesões em jogadores de futsal portugueses

INTRODUÇÃO: A reduzida expressão de estudos publicados sobre a incidência de lesões no Futsal em Portugal justificou a realização deste trabalho. OBJETIVO: Identificar as potenciais causas de lesões nesta modalidade, referência para o desenvolvimento de protocolos específicos de prevenção de lesões. MÉTODOS: A amostra foi constituída por 411 jogadores federados de Futsal em Portugal, masculinos e femininos, de diferentes níveis competitivos. Foram utilizados os dados coletados num questionário com informação retrospectiva. O tratamento estatístico consistiu na análise inferencial entre grupos através do teste de Kruskal-Wallis e do teste para dados não paramétricos de Mann-Whitney (nível de significância de 5%). RESULTADOS: Os resultados confirmaram a entorse da articulação tíbio-társica como a lesão de maior incidência (48,8% do total) no Futsal. As lesões com período de impedimento entre oito e 28 dias tiveram a maior expressão (52,7% do total). Este estudo não revelou diferenças significativas em relação ao gênero ou posição em que os jogadores ocupam na quadra sobre a incidência, o tipo ou a região anatômica das lesões. No entanto, verificou-se significativamente maior incidência de entorses e contraturas em situação de treino e maior incidência de roturas musculares e fraturas em jogo, sendo que essas últimas provocaram um período de impedimento maior para os atletas. Também se verificou significativamente maior incidência de lesões articulares ou ósseas, entorses e fraturas, em resultado do contato com adversários e maior incidência de lesões musculares ou ligamentares sem contato com adversários. Os resultados não evidenciaram diferenças significativas na lateralidade das lesões. CONCLUSÃO: Os resultados realçam a importância de programas específicos de prevenção da entorse da tíbio-társica, especialmente nas crianças e jovens, independentemente da posição que ocupam na quadra, particularmente em situações de contato com adversários

ETOP and its role in lung cancer research in Europe

Over the past 10 years, the treatment for lung cancer has drastically changed from chemotherapy - as the unique sole modality - to targeted therapies, immunotherapy and refinement of complex multimodality treatments. The de- velopment of targeted therapies and potent agents such as tyrosine kinase inhibitors shifted the therapeutic approach towards personalised medicine, where patients are treated in the context of their driver mutation

Morphological and functional assessment of the flexor carpi radialis brevis using conventional ultrasound and elastography.

The flexor carpi radialis brevis (FCRB) is a supernumerary musculotendinous structure of the wrist that has been the focus of some interest in the last decade. While its anatomy is well known, its in vivo function remains unknown as it has never been studied. Eleven cases of FCRB underwent a multimodal ultrasound consisting of B-mode, color Doppler and shear wave elastography. A pennate shape was observed in all cases and the mean value of the cross-sectional area was 0.8 cm <sup>2</sup> (SD 0.3 cm <sup>2</sup> ). Young's modulus was significantly (p < 0.01) different between the resting position and active flexion or passive extension. Our study demonstrates that the FCRB shows biomechanics of a typical skeletal muscle and is voluntarily controlled by flexing the wrist. Absent in other vertebrate taxa, the FCRB probably plays a role in active stability of the wrist in Human

Development of an In-Line Capable Sputtering Process of Silicon Nitride for Crystalline Silicon Solar Cells

The purpose of this work is to develop a high rate sputtering process for the deposition of silicon nitride antireflection coatings for crystalline silicon solar cells. Our goal is to achieve a cycle time that allows for the processing of single wafers without a reduction of the production line throughput. We have varied several processing parameters such as process gas composition and individual gas flows into the process chamber as well as different deposition rates. In order to assess the performance of the deposited layers with respect to their passivation quality complete cells were processed on monocrystalline Czochralski wafers (125x125 mm2). We have found that the implementation of molecular hydrogen as a process gas has a detrimental effect on the passivation quality of the deposited layers. Furthermore, a clear influence of the sputtering rate on the overall cell performance can be seen. We have achieved a cell efficiency of 17.5% applying a standard screen printed process

Afatinib in NSCLC With HER2 Mutations: Results of the Prospective, Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP)

Introduction: Mutations in erb-b2 receptor tyrosine kinase 2 (HER2)oncogene are observed in approximately 3% of lung adenocarcinomas or mixed tumors with adenocarcinoma component. Activity of various biologically distinct HER2 inhibitors, including the pan-HER inhibitor afatinib, has been reported in several retrospective trials or small series in advanced pretreated NSCLC with HER2 mutations. We report the first prospective evaluation of afatinib for the treatment of this molecularly defined entity. Methods: NICHE, a single-arm phase II trial using a two-stage Simon's design, explored the potential of afatinib to control disease in pretreated patients with advanced NSCLC harboring HER2 exon 20 mutations. A total of 13 patients entered the trial and were treated with afatinib 40 mg/day until tumor progression or lack of tolerability. Results: The first-stage stopping boundary was crossed when five of nine patients did not achieve disease control at 12 weeks. The accrual into the trial was stopped with total 13 patients enrolled, with 7 (53.8%)achieving disease control at 12 weeks. Except for 1 patient with early death, progression was documented for all patients, with median progression-free survival of 15.9 weeks (95% confidence interval: 6.0–35.4), and median overall survival of 56.0 weeks (95% confidence interval: 16.3– upper limit not estimable). The toxicity profile was in the expected range. Conclusions: Afatinib did not show the expected potential for disease control in NSCLC. However, more than half of the patients in the full cohort achieved disease control at 12 weeks. © 2019 International Association for the Study of Lung Cance

Monoubiquitination and Activity of the Paracaspase MALT1 Requires Glutamate 549 in the Dimerization Interface.

The mucosa-associated lymphoid tissue protein-1 (MALT1, also known as paracaspase) is a protease whose activity is essential for the activation of lymphocytes and the growth of cells derived from human diffuse large B-cell lymphomas of the activated B-cell subtype (ABC DLBCL). Crystallographic approaches have shown that MALT1 can form dimers via its protease domain, but why dimerization is relevant for the biological activity of MALT1 remains largely unknown. Using a molecular modeling approach, we predicted Glu 549 (E549) to be localized within the MALT1 dimer interface and thus potentially relevant. Experimental mutation of this residue into alanine (E549A) led to a complete impairment of MALT1 proteolytic activity. This correlated with an impaired capacity of the mutant to form dimers of the protease domain in vitro, and a reduced capacity to promote NF-κB activation and transcription of the growth-promoting cytokine interleukin-2 in antigen receptor-stimulated lymphocytes. Moreover, this mutant could not rescue the growth of ABC DLBCL cell lines upon MALT1 silencing. Interestingly, the MALT1 mutant E549A was unable to undergo monoubiquitination, which we identified previously as a critical step in MALT1 activation. Collectively, these findings suggest a model in which E549 at the dimerization interface is required for the formation of the enzymatically active, monoubiquitinated form of MALT1