How are normal sleeping controls selected? A systematic review of cross-sectional insomnia studies, and a standardised method to select healthy controls for sleep research

There appears to be some inconsistency in how normal sleepers (controls) are selected and screened for participation in research studies for comparison with insomnia patients. The purpose of the current study is to assess and compare methods of identifying normal sleepers in insomnia studies, with reference to published standards. We systematically reviewed the literature on insomnia patients which included control subjects. The resulting 37 articles were systematically reviewed with reference to the five criteria for normal sleep specified by Edinger et al. (2004). In summary, these criteria are: evidence of sleep disruption; sleep scheduling; general health; substance/medication use; and other sleep disorders. We found sleep diaries, PSG, and clinical screening examinations to be widely used with both control subjects and insomnia participants. However, there are differences between research groups in the precise definitions applied to the components of normal sleep. We found that none of reviewed studies applied all of the Edinger et al. criteria, and 16% met four criteria. In general, screening is applied most rigorously at the level of a clinical disorder, whether physical, psychiatric, or sleep. While the Edinger et al. criteria seem to be applied in some form by most researchers, there is scope to improve standards and definitions in this area. Ideally, different methods such as sleep diaries and questionnaires would be used concurrently with objective measures to ensure normal sleepers are identified, and descriptive information for control subjects would be reported. Here, we have devised working criteria and methods to be used for assessment of normal sleepers. This would help clarify the nature of the control group, in contrast to insomnia subjects and other patient groups

The inhibition of FGF receptor 1 activity mediates sorafenib-induced antiproliferative effects in human mesothelioma tumor-initiating cells

Tumor-initiating cells (TICs), the subset of cells within tumors endowed with stem-like features, being highly resistant to conventional cytotoxic drugs, are the major cause of tumor relapse. The identification of molecules able to target TICs remains a significant challenge in cancer therapy. Using TIC-enriched cultures (MM1, MM3 and MM4), from 3 human malignant pleural mesotheliomas (MPM), we tested the effects of sorafenib on cell survival and the intracellular mechanisms involved. Sorafenib inhibited cell-cycle progression in all the TIC cultures, but only in MM3 and MM4 cells this effect was associated with induction of apoptosis via the down-regulation of Mcl-1. Although sorafenib inhibits the activity of several tyrosine kinases, its effects are mainly ascribed to Raf inhibition. To investigate the mechanisms of sorafenib-mediated antiproliferative activity, TICs were treated with EGF or bFGF causing, in MM3 and MM4 cells, MEK, ERK1/2, Akt and STAT3 phosphorylation. These effects were significantly reduced by sorafenib in bFGF-treated cells, while a slight inhibition occurred after EGF stimulation, suggesting that sorafenib effects are mainly due to FGFR inhibition. Indeed, FGFR1 phosphorylation was inhibited by sorafenib. A different picture was observed in MM1 cells, which, releasing high levels of bFGF, showed an autocrine activation of FGFR1 and a constitutive phosphorylation/activation of MEK-ERK1/2. A powerful inhibitory response to sorafenib was observed in these cells, indirectly confirming the central role of sorafenib as FGFR inhibitor. These results suggest that bFGF signaling may impact antiproliferative response to sorafenib of MPM TICs, which is mainly mediated by a direct FGFR targeting

Attention to beds in natural scenes by observers with insomnia symptoms

Attention biases to sleep-related stimuli are held to play a key role in the development and maintenance of insomnia, but such biases have only been shown with controlled visual displays. This study investigated whether observers with insomnia symptoms allocate attention to sleep-related items in natural scenes, by recording eye movements during free-viewing of bedrooms. Participants with insomnia symptoms and normal sleepers were matched in their visual exploration of these scenes, and there was no evidence that the attention of those with insomnia symptoms was captured more quickly by sleep-related stimuli than that of normal sleepers. However, the insomnia group fixated bed regions on more trials and, once fixated on a bed, also remained there for longer. These findings indicate that sleep stimuli are particularly effective in retaining visual attention in complex natural scenes

Tobacco exposure and sleep disturbance in 498 208 UK Biobank participants

Background: The prevalence of sleep disturbance is high and increasing. The study investigated whether active, former and passive smoking were associated with sleep disturbance. Methods: This cross-sectional study used data from the UK Biobank: a cohort study of 502 655 participants, of whom 498 208 provided self-reported data on smoking and sleep characteristics. Multivariable multinomial and logistic regression models were used to examine the associations between smoking and sleep disturbance. Results: Long-sleep duration (>9 h) was more common among current smokers [odds ratio (OR): 1.47; 95% confidence interval (CI): 1.17–1.85; probability value (P) = 0.001] than never smokers, especially heavy (>20/day) smokers (OR: 2.85; 95% CI: 1.66–4.89; P < 0.001). Former heavy (>20/day) smokers were also more likely to report short (<6 h) sleep duration (OR: 1.41; 95% CI: 1.25–1.60; P < 0.001), long-sleep duration (OR: 1.99; 95% CI: 1.47–2.71; P < 0.001) and sleeplessness (OR: 1.47; 95% CI: 1.38–1.57; P < 0.001) than never smokers. Among never smokers, those who lived with more than one smoker had higher odds of long-sleep duration than those not cohabitating with a smoker (OR: 2.71; 95% CI: 1.26–5.82; P = 0.011). Conclusions: Active and passive exposure to high levels of tobacco smoke are associated with sleep disturbance. Existing global tobacco control interventions need to be enforced

Circulating cell-free DNA and circulating tumor cells as prognostic and predictive biomarkers in advanced non-small cell lung cancer patients treated with first-line chemotherapy

Cell-free DNA (cfDNA) and circulating tumor cells (CTCs) are promising prognostic and predictive biomarkers in non-small cell lung cancer (NSCLC). In this study, we examined the prognostic role of cfDNA and CTCs, in separate and joint analyses, in NSCLC patients receiving first line chemotherapy. Seventy-three patients with advanced NSCLC were enrolled in this study. CfDNA and CTC were analyzed at baseline and after two cycles of chemotherapy. Plasma cfDNA quantification was performed by quantitative PCR (qPCR) whereas CTCs were isolated by the ScreenCell Cyto (ScreenCell, Paris, France) device and enumerated according to malignant features. Patients with baseline cfDNA higher than the median value (96.3 hTERT copy number) had a significantly worse overall survival (OS) and double the risk of death (hazard ratio (HR): 2.14; 95% confidence limits (CL) = 1.24\u20133.68; p-value = 0.006). Conversely, an inverse relationship between CTC median baseline number (6 CTC/3 mL of blood) and OS was observed. In addition, we found that in patients reporting stable disease (SD), the baseline cfDNA and CTCs were able to discriminate patients at high risk of poor survival. cfDNA demonstrated a more reliable biomarker than CTCs in the overall population. In the subgroup of SD patients, both biomarkers identified patients at high risk of poor prognosis who might deserve additional/alternative therapeutic interventions

Essays in international trade and organisational economics

This thesis contains three chapters that examine various facets of how the market and technological environment shapes firms – and how firms shape their environments. The first chapter studies how multinational manufacturing firms organise production in parallel processing supply chains. Using confidential data on international sourcing of French manufacturing firms and an instrumental variables strategy based on selfconstructed input-output tables, the chapter shows that inputs that account for a high cost share – i.e. that are more important for technological reasons – are more likely to be produced by a multinational for itself, while unimportant ones are outsourced to third parties. It provides additional empirical evidence that this main finding is consistent with a property rights model of the boundary of the firm. The second chapter produces empirical facts on how exogenous changes in tariffs on intermediate goods have affected vertical integration patterns in France over the period 1996-2006 and evaluates them in light of the current literature. Using a long differences approach and detailed information on supply relationships, it shows that more protectionist policies by other countries and by the EU discouraged integrated relationships from shifting towards outsourcing and that initial market structure mattered for the impact of trade policy. The third chapter provides rare causal evidence for the relevance of endowment driven comparative advantage. It uses the fracking boom in the US following 2006 as a source of exogenous variation in the endowment of natural gas – and therefore in energy: fracking made energy considerably cheaper in the US compared to the rest of the world. The chapter studies factor, output, and international trade responses across sectors. It finds that energy intensive sectors expand along all dimensions and, most importantly, export more, which validates one of the most important neo-classical theories of why countries trade with each other

Anthropocene and "development" : intertwined trajectories since the beginning of the Great Acceleration = Antropoceno e "desenvolvimento" : trajetórias entrelaçadas desde o começo da Grande Aceleração

Objectives: We aim to propose the thesis that the trajectories of the Anthropocene and the current mainstream understandings of development are intertwined from the beginning. It means that the Anthropocene and the “development” are coetaneous: the implementation of development policies for the so-considered underdeveloped regions started to happen at the same time of what is known as The Great Acceleration of production, consumption and environmental degradation in a global level. Method: In this conceptual paper, we adopt a decolonial critique as an analytical lens and argue that different geopolitical positions may be necessary for approaching the issue of the Anthropocene from epistemological reflections that can include the cultural and political context of the production and reproduction of local knowledge. Results: Our theoretical argumentation sheds light on the role of Global North and South relations in shaping the environmental crisis. Latin America (LA) exemplifies the modus operandi of the intertwinement of the practical effects of development policies and the environmental consequences underlying the Anthropocene, in which natural resources are over-explored to satisfy export-oriented trade, from the South toward the North. LA is not only a propitious context to show the validity of our thesis, but also the source of alternatives to such developmental model. Conclusion: The emphasis on development as a cause of the Anthropocene supports The Great Acceleration thesis. The proposition of the name Developmentocene comes from the thesis that development and Anthropocene are coetaneous, the intertwinement of both resulting in the very definition of the new epoch.Objetivo: Buscamos propor a tese de que as trajetórias do Antropoceno e o entendimento atualmente dominante sobre desenvolvimento estão entrelaçadas desde o começo. Isso implica que o Antropoceno e o “desenvolvimento” são coetâneos: a implementação de políticas de desenvolvimento em regiões tidas como subdesenvolvidas começou a acontecer ao mesmo tempo em que teve início A Grande Aceleração da produção, do consumo e da degradação ambiental em nível global. Método: Neste artigo conceitual, nós adotamos a crítica decolonial como lente analítica e argumentamos a necessidade de diferentes posições geopolíticas para abordar a questão do Antropoceno a partir de reflexões epistemológicas que possam incluir o contexto cultural e político de produção e reprodução do conhecimento. Resultados: Nossa argumentação teórica enaltece as relações entre o Norte e o Sul Global no delineamento da crise ambiental. A América Latina (AL) exemplifica o modus operandi do entrelaçamento entre os efeitos práticos das políticas de desenvolvimento e as consequências ambientais subjacentes ao Antropoceno, em que os recursos naturais são explorados além dos limites para satisfazer o comércio para exportações, desde o Sul para o Norte. Nesse quadro, a AL não é apenas um contexto propício para mostrar a validade da nossa tese, mas também a fonte de alternativas a esse modelo de desenvolvimento. Conclusão: A ênfase no desenvolvimento como causa do Antropoceno apoia a tese da Grande Aceleração. A proposição do nome Desenvolvimentoceno advém da tese de que o desenvolvimento e o Antropoceno são coetâneos e que o entrelaçamento de ambos resulta na própria definição da nova época