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“The work is everything,” says Ben, the main character of McCarthy's play The Stonemason, summing up his grandfather Papaw's view of the craft of the stonemason as the ground of beauty, justice, and truth. Judging from McCarthy's inclination to indulge in extended descriptions of all sorts of labors and crafts he must, at least in part, agree with his character. As has been noted elsewhere, craftsmanship is a privileged theme in Cormac McCarthy's oeuvre, and the available archival material proves that the author has always been meticulous in gathering information about the crafts he has set himself to describe, undertaking extensive bibliographical research in all technical aspects and at times seeking help from specialist advisers. Relying on some manuscripts and letters held at the Wittliff Collections in San Marcos, Texas, this article investigates the way McCarthy collaborated with two specialist medical advisers, Dr. Oren Ellis and Dr. Barry King, in the writing of a scene of his novel The Crossing. The intention is to provide insight into McCarthy's creative process and to further understand the way descriptions of crafts integrate within his overall poetics in what can be defined as an attempt to oversaturate the representation of reality.

Architectural spaces are usually considered only in their visual and threedimensional character. However, the proper experience of space is multisensory. Sonority is undoubtedly the non-visual characteristic that most affects architecture, influencing its three-dimensional shape, and the size and distribution of its individual parts. Early modern sacred architecture is a case in point. Focusing on Rome and the development of architecture in relation to musical practices, this article demonstrates how architectural forms evolved through a process that ranged from provisional installations to the design of entirely new churches and oratories. In the Baroque period, these religious structures were conceived as synaesthetic spaces of sonority and architecture, in which vision, hearing and liturgical acts merged in an expressive unity.

The importance of place – as a unique spatial identity – has been recognized since antiquity. Ancient references to the 'genius loci', or spirit of place, evoked not only the location of a distinct atmosphere or environment, but also the protection of this location, and implicitly, its making and construction. This volume examines the concept of place as it relates to architectural production and building knowledge in early modern Europe (1400-1800). The places explored in the book's ten essays take various forms, from an individual dwelling to a cohesive urban development to an extensive political territory. Within the scope of each study, the authors draw on primary source documents and original research to demonstrate the distinctive features of a given architectural place, and how these are related to a geographic location, social circumstances, and the contributions of individual practitioners. The essays underscore the distinct techniques, practices and organizational structures by which physical places were made in the early modern period.

Introduction: Interstitial lung diseases (ILD) are a heterogeneous group of diseases characterized by inflammation and/or fibrosis. Small airways ( Objectives: Assess small airways involvement through IOS in patients with ILD. Assess a possible correlation between small airways resistance, reactance and symptoms. Assess a possible correlation between the values R5-R20 and the degree of small airways involvement in HRTC. Methods: A single-center prospective cohort study. Patients with different diagnoses of ILD were divided in two subgroups: fibrosing ILD and non-fibrosing ILD. They underwent spirometry, HRTC and IOS. Parameters collected were: R5 (total airway resistance), R20 (central airway resistance); R5-R20 (small airway resistance), AX (reactance area), X5 (reactance measured at a 5 Hertz frequency). Results: 70 patients with a diagnosis of ILD have been enrolled: 33 with fibrosing ILD, 37 with non-fibrosing ILD. The fibrosing ILD group has R5-R20 higher than non-fibrosing ILD group statistically significant and in fibrosing ILD group R5-R20 increases with the age of patients. In fibrosing ILD there is a inverse statistically significant correlation of X5 with the FVC % predicted. In non-fibroing ILD, the thickening of the bronchiolar walls is associated with an increase in R5-R20 statistically significant. Conclusion: IOS could be useful in ILD to value the small airways involvement together with HRCT. Reactance could have a role in the functional follow-up of fibrosing ILD patients.

Summary Background Whether blood eosinophil counts and exhaled nitric oxide (FeNO) are associated with important outcomes in mild asthma is unclear. In this prespecified subgroup analysis of a previously published open-label clinical trial, we aimed to assess associations between blood eosinophil counts and FeNO with outcomes and response to asthma treatment. Methods In the previously reported 52-week, open-label, randomised controlled trial, people with mild asthma receiving only β agonist reliever inhalers were enrolled at one of 16 clinical trials units in New Zealand, the UK, Italy, or Australia. Eligible participants were randomly assigned (1:1:1, stratified by country), to receive inhalers to take as-needed salbutamol (two inhalations of 100 μg in a pressurised metered dose inhaler), maintenance budesonide (200 μg twice per day by inhaler) plus as-needed salbutamol (two inhalations of 100 μg), or as-needed budesonide–formoterol (one inhalation of 200 μg budesonide and 6μg formoterol by inhaler). The primary outcome was the annual rates of asthma exacerbations per patient, and in this prespecified subgroup analysis, we assessed whether annual exacerbation rates in each treatment group were significantly different depending on levels of blood eosinophil count, FeNO, or a composite score of both. Analyses were done for patients with available biomarker measurements The study was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12615000999538. Findings 675 participants were enrolled between March 17, 2016, and Aug 29, 2017, of whom 656 had results for blood eosinophil analysis and 668 had results for FeNO. Of the patients who received as-needed salbutamol, the proportion of patients having a severe exacerbation increased progressively with increasing blood eosinophil count (two [4%] of 49 participants with Interpretation In patients with mild asthma, the effects of as-needed budesonide–formoterol on exacerbations are independent of biomarker profile, whereas the benefits of maintenance inhaled budesonide are greater in patients with high blood eosinophil counts than in patients with low counts. Funding AstraZeneca, Health Research Council of New Zealand.

Introduction: small-airway impairments contribute to the severity of the clinical manifestation of asthma. Small airway abnormalities are key elements in the pathogenesis of COPD Aims: to evaluate small-airway impairment in patients with severe asthma (SA), moderate controlled asthma (CA) and COPD. To evaluate correlation between small airway abnormalities and symptoms in these patients Methods: COPD (n=21), SA patients (n=35; of which 45% treated with monoclonal antibody biological therapies) and CA patients (n=19) matched for age, gender and degree of pre¬bronchodilator airflow obstruction were enrolled into the study. The inhomogeneity of small airways ventilation was evaluated by SBNWT (dN2) phase 3 slope and the contribution of small airways resistance by iOS (R5¬R20). Patients were asked to record daily symptom severity scores for dyspnoea, sputum and cough. The use of rescue medication (puffs/week) was also recorded Results: In SA patients dN2 and R5-R20 levels were significantly higher compare to CA patients (p Conclusions: Higher level of small-airway impairment was found in COPD compare to asthma. Among asthmatics, the small-airway impairment was significantly higher in SA and in particular in patients not receiving biologics. In SA patients the magnitude of small-airway impairment correlated with the severity of the clinical manifestation of the disease

The last decade has seen a veritable resurgence of the theme of habit in philosophical and critical debates. While for decades the preference had been accorded to either the active forces of will and desire or the contingency and abruptness of the Event, thinkers have recently come back to habit from different paths and perspectives (Bennett et al.; Sparrow and Hutchinson; Carlisle). The polarization of attention around the theme of habit almost seems to mirror the veritable explosion of the discourse on habit which took place about two centuries ago. Even though the philosophical reflection on habit can be traced at least as far back as Aristotle it was at the end of the eighteenth century and in the early nineteenth century that the theme of habit, as asserted in the entry habitude of the Encyclopedie Philosophique Universelle, became "a new philosophical challenge" as an effect of "the refusal of innate ideas; the sensualist project deriving the modes of understanding from experience (generally exterior experience); the refusal, finally, of Hume's category of causality and its reduction to pure habit" (1108; my translation). In France, habit was an extremely popular theme among spiritualist or proto-spiritualist philosophers such as Maine de Biran and Ravaisson, who considered it the bridge between spirit and matter. In Germany, Hegel tackled the problem of habit in The Philosophy of Right, making it the basis of custom on which a true ethical life is grounded. In Italy, reprehensible antisocial habits fell under the magnifying glass of the Turin positivist school and became a pivotal part of Lombroso's analysis of the criminal mind. In the English speaking world, Samuel Butler (1835-1902) was probably the most original contributor to the debate on habit in the second part of the nineteenth century. He used the notion of habit to challenge Charles Darwin's theory of evolution, conceiving habit as the channel through which unconscious memory can be passed down from one generation to the next, preserved in the experience of the species and its determination to evolve into more complex forms (see Willey). Samuel Butler's theories have been widely disregarded among professional philosophers, because of his idiosyncratic and counter-intuitive use of the notion of habit and due to the fact that his arguments have often been seen as amateurish. Nonetheless, several leading twentieth-century thinkers, such as Gregory Bateson and Gilles Deleuze, have repeatedly extolled the visionary power of Butler's ideas and admitted their debts towards them. Moreover, Butler's theories of habit were influential among several modernist writers, such as H. G. Wells, Virginia Woolf, Valery Larbaud, and E. M. Forster and they contributed both to these authors' understanding of the crisis of modern subjectivity and to their attention for the representation of habitual behavior and the everyday. In this paper I intend to demonstrate how Butler's theory of habit--in particular as it is presented in his seminal work Life and Habit--once it is disentangled from the anti-Darwinian debates on the theory of evolution from which it first emerged, can offer a considerable contribution to the contemporary philosophical debate and allow a better understanding of the history of the idea of habit at the turn of the century. Moreover, I intend to show how the import of these ideas was promptly acknowledge by several modernist writers, who turned to Butler in an effort to investigate the habitual side of life through their characters. In doing so, they were moved by the belief that the modern ethos, as well as the modern idea of subjectivity, could find their proper mode of expression precisely in that previously neglected dimension of life. Butler's theory of habit stems from the heated late nineteenth-century debate concerning Darwinism and the theory of evolution. Charles Darwin's On the Origin of Species (Willey 70 and ff.) had a pivotal influence on Butler's life and thought, determining his abandonment of the Christian faith and his conversion to agnosticism. …

Alvise Cornaro’s Treatises on the Sober Life (Discorsi della vita sobria) was one of the most popular books on diet and hygiene across the whole of Europe from its publication in the sixteenth century up to the early twentieth century. In this chapter, I show that the reasons for the success of Cornaro’s work in early modern England lie in the fact that two very different communities of practice saw the work’s conclusions as grounded upon a particular configuration of evidence that resonated with them: one spiritual, where it was used as part of an attempt to forge a via media between Puritans and Anglicans; the other medical, where it served as a case study from which more general conclusions about how to prolong life might be extrapolated. The unique context in which the first English translation of the Discorsi was conceived, produced, and published—involving some of the most prominent intellectual figures of the time, such as Francis Bacon, Nicholas Ferrar, and George Herbert—make this an important case study, useful for the reconstruction of a significant chapter of the history of dieting and hygiene, and the history of conceptions of evidence and their relationship to different communities of practice.

In this essay, I read Moby-Dick as an allegorical description of the process of Ishmael's healing from melancholy. Ishmael's inane reveries at the beginning of the story evolve into a productive and self-creative narrative power. His initial melancholy reverie is represented in the novel as the narcissistic tendency of the subject to withdraw into oneself and sink into its own interiority, as well as the tendency to believe in a sentimental universal brotherhood. Ishmael manages to get free of his sterile daydreaming and regain contact with reality through a close experience of mortality and the confrontation with the power and complexity of writing.

Cigarette smoking enhances small airways impairment in asthmatic patients http://ow.ly/WWUky

Nicola Scichilone,1 Alida Benfante,1 Luca Morandi,2 Federico Bellini,2 Alberto Papi21Biomedical Department of Internal and Specialist Medicine, Section of Pulmonology, University of Palermo, Italy; 2Respiratory Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, ItalyAbstract: Asthma and chronic obstructive pulmonary disease (COPD) are among the most common chronic diseases worldwide, characterized by a condition of variable degree of airway obstruction and chronic airway inflammation. A large body of evidence has demonstrated the importance of small airways as a pharmacological target in these clinical conditions. Despite a deeper understanding of the pathophysiological mechanisms, the epidemiological observations show that a significant proportion of asthmatic and COPD patients have a suboptimal (or lack of) control of their diseases. Different factors could influence the effectiveness of inhaled treatment in chronic respiratory diseases: patient-related (eg, aging); disease-related (eg, comorbid conditions); and drug-related/formulation-related factors. The presence of multiple illnesses is common in the elderly patient as a result of two processes: the association between age and incidence of degenerative diseases; and the development over time of complications of the existing diseases. In addition, specific comorbidities may contribute to impair the ability to use inhalers, such as devices for efficient drug delivery in the respiratory system. The inability to reach and treat the peripheral airways may contribute to the lack of efficacy of inhaled treatments. The recent development of inhaled extrafine formulations allows a more uniform distribution of the inhaled treatment throughout the respiratory tree to include the peripheral airways. The beclomethasone/formoterol extrafine formulation is available for the treatment of asthma and COPD. Different biomarkers of peripheral airways are improved by beclomethasone/formoterol extrafine treatment in comparison with equivalent nonextrafine inhaled corticosteroids/long-acting beta-2 agonist (ICS/LABA) combinations. These improvements are associated with improved lung function and clinical outcomes, along with reduced systemic exposure to inhaled corticosteroids. The increased knowledge in the pathophysiology of the peripheral airways may lead to identify specific phenotypes of obstructive lung diseases that would mostly benefit from the treatments specifically targeting the peripheral airways.Keywords: COPD, asthma, inhalational therapy, small airways

Randomized Controlled Trials (RCTs) are the "gold standard" for evaluating treatment outcomes providing information on treatments "efficacy". They are designed to test a therapeutic hypothesis under optimal setting in the absence of confounding factors. For this reason they have high internal validity. The strict and controlled conditions in which they are conducted, leads to low generalizability because they are performed in conditions very different from real life usual care. Conversely, real life studies inform on the "effectiveness" of a treatment, that is, the measure of the extent to which an intervention does what is intended to do in routine circumstances. At variance to RCTs, real life trials have high generalizability, but low internal validity. Recently the number of real life studies has been rapidly growing in different areas of respiratory medicine, particularly in asthma and COPD. The role of such studies is becoming a hot topic in respiratory medicine, attracting research interest and debate. In the first part of this review we discuss some of the advantages and disadvantages of different types of RCTs and analyze the strengths and weaknesses of real life trials, considering the recent examples of some studies conducted in COPD. We then discuss methodological approaches and options to overcome some of the limitations of real life studies. Comparing the conclusions of effectiveness and efficacy trials can provide important pieces of information. Indeed, these approaches can result complementary, and they can guide the interpretation of each other results.