Comparison of Dry-Powder Inhaler and Pressurized Metered-Dose Inhaler Formulations of Extrafine Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium in Patients with COPD: The TRI-D Randomized Controlled Trial

Background: Three 52-week studies in COPD have assessed the efficacy and safety of single-inhaler extrafine formulation triple therapy combining beclomethasone dipropionate (BDP), formoterol fumarate (FF) and glycopyrronium (G) delivered via pressurized metered-dose inhaler (pMDI). BDP/FF/G is now being developed for delivery via multi-dose dry-powder inhaler (DPI; NEXThaler). This study aimed to demonstrate non-inferiority of BDP/FF/G DPI vs pMDI for lung function. Methods: Multicenter, randomized, double-blind, double-dummy, active-controlled, three-way cross-over study in patients with COPD and post-bronchodilator forced expiratory volume in 1 second (FEV1) 30-80% predicted. Patients received BDP/FF/G 100/6/10 mu g via DPI and pMDI, and BDP/FF 100/6 mu g via pMDI, all two inhalations twice daily for four weeks, with treatments separated by two-week washout. The two co-primary objectives were to demonstrate non-inferiority between the two BDP/FF/G formulations for FEV1 area under the curve between 0 and 12 hours post-dose (AUC(0-12h)) normalized by time and trough FEV1 at 24 hours, both on Day 28. EudraCT 2017-004405-41. Results: Of 449 patients screened, 366 were randomized, with 342 (93.4%) completing all three treatment periods. The primary objectives were met, with changes from baseline in FEV1 AUC(0-1)(2h) and trough FEV1 on Day 28 similar for the two BDP/FF/G formulations, and the confidence intervals for the difference lying entirely within the pre-specified non-inferiority criterion (-50mL): -20 (-35, -6) mL and 3 (-15, 20) mL for AUC(0-12h) and trough FEV1, respectively. BDP/FF/G pMDI and DPI were statistically superior to BDP/FF for these endpoints (p<0.001). A similar proportion of patients experienced adverse events with each treatment (15.5%, 18.7% and 15.4% with BDP/FF/G DPI and pMDI, and BDP/FF, respectively); the majority were mild or moderate, with few related to treatment. Conclusion: Extrafine BDP/FF/G DPI and pMDI demonstrated similar efficacy and safety in patients with COPD, supporting the DPI formulation as a valid alternative

Heavy Flavour Working Group Summary

We review theoretical and phenomenological aspects of heavy flavour production as discussed in the heavy flavour working group of the DIS 2012. Recent theoretical progress includes approximate NNLO calculations for heavy quark structure functions in deep inelastic scattering, the extension of the ACOT heavy flavour scheme to jet production, and advances in top physics where the highlight is clearly the first complete NNLO QCD prediction for top pair production in the $q \bar{q}$ annihilation channel. Furthermore, state of the art phenomenological predictions for open charm and bottom, charmonium, and single top and top pair production are discussed in addition to other topics such as the effect of double parton scattering on heavy quark production. New measurements on charm and beauty production presented in the heavy flavor working group are summarized and discussed in comparison with QCD predictions. Top quark strong and weak couplings as well as top quark properties are being measured with precision at the LHC and the Tevatron. We summarize also recent results on spectroscopy of charmonia, bottomonia and $b$-hadrons, along with studies of their decays and properties. Searches for physics beyond Standard Model through precise measurements of rare decays of heavy flavours are discussed as well.Comment: 16 pages, 5 figures, to be published in the Proceedings of the XX International Workshop on Deep Inelastic Scattering, University of Bonn, 26-30th March 201

heavy flavours in dis using muon tags at hera

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Edoardo Benvenuto Prize. Collection of papers

The promotion of studies and research on the science and art of building in their historical development constitutes the objective that the Edoardo Benvenuto Association has set itself, since its establishment, in order to honor the memory of Edoardo Benvenuto (1940-1998). The Association in recent years has achieved interesting results by developing various activities such as: organization of national and international meetings, conferences, study days; collaborations with national and foreign research institutions; promotion of the editorial series “Between Mechanics and Architecture"; activation of the portal Bibliotheca Mechanica Architectonica, first “open source” digitized library dedicated to historical research on mechanical and architectural texts. But perhaps the most qualifying initiative was the institution of the Edoardo Benvenuto Prize, arrived in 2019 in its twelfth edition, reserved for young researchers in the field of historical studies on science and the art of building. The awarding of the Prize takes place after an in-depth examination of the texts received by the Association by an international commission of experts. The purpose of this book is to collect and present the most recent studies and publications produced by the winners of the various editions of the Edoardo Benvenuto Prize

Occupational Hazards in veterinarians: an updating.

Background: The veterinarian is a complex and varied work: risks in veterinary activity show are more typical of manual work than medical profession. Many reviews analyzed occupational risks related to veterinarians, but compared to the past current risks are more different. This review analyzes veterinary profession considering main occupational risk factors, as defined by World Health Organization: physical, chemical, biological or other agents that may cause harm to an exposed person in the workplace and is potentially modifiable. Methods: Publications investigating physical, chemical, biological, cancer and stress risk as well as effects associated with these exposures through veterinary practice were searched in the PubMed and Web of Science database. Publications were judged to be covered in the review when the following inclusion criteria applied: Articles should be published in the English language; Articles published after 2000; Studies reporting some numerical data about exposures and subjects considered; Studies concerning health effects regarding only veterinarians associated with exposure to animals, not general population. Results: Compared to the past, when the main risk of occupational disease was represented by zoonosis (in particular mycotic infections, mange, swine erysipelas, anthrax and tuberculosis), current risks are also represented by new entities such as mental and physical stress. However injuries, radiations, chemicals, zoonosis and allergies continue to represent a considerable portion of professional risks. Conclusions: Zoonosis, injuries and trauma remain the main occupational risk for veterinarians today, but new emerging risks, such as psychological risks are becoming increasingly important for these workers

Work-related allergies to storage mites in Parma (Italy) ham workers

OBJECTIVES: To investigate the role of storage mites in the development of allergic diseases among ham production workers, and to search for early alterations in lung function tests and early inflammation markers in exhaled air. Respiratory allergies due to storage mites have been reported in people with various occupations but, although such mites are unavoidable when curing ham, there are no published data concerning ham production workers. SETTING: Secondary care. DESIGN: Experimental cross-sectional study. PARTICIPANTS: 220 participants (110 ham production workers and 110 controls) were recruited. PRIMARY AND SECONDARY OUTCOME MEASURES: Workers answered a medical questionnaire, and underwent spirometry and fraction of exhaled nitric oxide at 50 mL/s (FeNO50) measurements. Those with allergic symptoms also underwent skin prick tests to determine their sensitisation to airborne allergens. A methacholine test was performed in symptomatic participants when spirometry was normal to assess airways hyper-responsiveness. RESULTS: Symptomatic storage mite sensitisation was observed in 16 workers (14.5%) (rhinoconjunctivitis in 15 (63%) and asthma in (4%)) and 2 controls (1.8%; p=0.001). Higher FeNO50 values in exposed symptomatic workers compared with healthy control participants (34.65±7.49 vs 13.29±4.29 ppb; p<0.001) suggested bronchial and nasal involvement, although their lung function parameters were normal. Regardless of exposure, a FeNO50 value of 22.5 ppb seems to be 100% sensitive and 99.4% specific in distinguishing allergic and non-allergic participants. Multivariate analysis of FeNO50 values in the symptomatic participants showed that they were positively influenced by IgE-mediated allergy (p=0.001) and reported symptom severity (p=0.041), and negatively by smoking status (p=0.049). CONCLUSIONS: Ham processing workers, as well as workers involved in any meat processing work that includes curing, should be informed about the occupational risk of sensitisation to mites

Gender differences and aging: Effects on the human heart

Objectives.This study investigated the changes in myocyte size and number in the left and right ventricles that occur with aging in the female and male heart.Background.Differences in life span between women and men may be related to a better preservation of myocardial structure in the female heart with aging. On this basis, the hypothesis was advanced that the aging process has a different impact on the integrity of the myocardium in the two genders.Methods.Morphometric methodologies were applied to analyze the changes in number and size of ventricular myocytes in the hearts of 53 women and 53 men. The changes in mononucleated and binucleated myocytes with age were determined in enzymatically dissociated cells. The age interval examined varied from 17 to 95 years.Results.Aging was associated with a preservation of ventricular myocardial mass, aggregate number of mononucleated and binucleated myocytes, average cell diameter and volume in the female heart. In contrast, nearly 1 g/year of myocardium was lost in the male heart, and this phenomenon accounted for the loss of ∼64 million cells. This detrimental effect involved the left and right sides of the heart. In the remaining cells, myocyte cell volume increased at a rate of 158 μm3/year in the left and 167 μm3/year in the right ventricle.Conclusions.Aging does not lead to myocyte cell loss and myocyte cellular reactive hypertrophy in women, indicating that gender differences may play a significant role in the detrimental effects of the aging process on the heart

The tissue inhibitor of metalloproteinases-1 (TIMP-1) promotes survival and migration of acute myeloid leukemia cells through CD63/PI3K/Akt/p21 signaling

We and others have shown that the Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), a member of the inflammatory network exerting pleiotropic effects in the bone marrow (BM) microenvironment, regulates the survival and proliferation of different cell types, including normal hematopoietic progenitor cells. Moreover, TIMP-1 has been shown to be involved in cancer progression. However, its role in leukemic microenvironment has not been addressed. Here, we investigated the activity of TIMP-1 on Acute Myelogenous Leukemia (AML) cell functions. First, we found that TIMP-1 levels were increased in the BM plasma of AML patients at diagnosis. In vitro, recombinant human (rh)TIMP-1 promoted the survival and cell cycle S-phase entry of AML cells. These kinetic effects were related to the downregulation of cyclindependent kinase inhibitor p21. rhTIMP-1 increases CXCL12-driven migration of leukemic cells through PI3K signaling. Interestingly, activation of CD63 receptor was required for TIMP-1's cytokine/chemokine activity. Of note, rhTIMP-1 stimulation modulated mRNA expression of Hypoxia Inducible Factor (HIF)-1a, downstream of PI3K/Akt activation. We then co-cultured AML cells with normal or leukemic mesenchymal stromal cells (MSCs) to investigate the interaction of TIMP-1 with cellular component(s) of BM microenvironment. Our results showed that the proliferation and migration of leukemic cells were greatly enhanced by rhTIMP-1 in presence of AML-MSCs as compared to normal MSCs. Thus, we demonstrated that TIMP-1 modulates leukemic blasts survival, migration and function via CD63/PI3K/ Akt/p21 signaling. As a "bad actor" in a "bad soil", we propose TIMP-1 as a potential novel therapeutic target in leukemic BM microenvironment

ADPKD: Prototype of Cardiorenal Syndrome Type 4

The cardiorenal syndrome type 4 (Chronic Renocardiac Syndrome) is characterized by a condition of primary chronic kidney disease (CKD) that leads to an impairment of the cardiac function, ventricular hypertrophy, diastolic dysfunction, and/or increased risk of adverse cardiovascular events. Clinically, it is very difficult to distinguish between CRS type 2 (Chronic Cardiorenal Syndrome) and CRS type 4 (Chronic Renocardiac Syndrome) because often it is not clear whether the primary cause of the syndrome depends on the heart or the kidney. Autosomal dominant polycystic kidney disease (ADPKD), a genetic disease that causes CKD, could be viewed as an ideal prototype of CRS type 4 because it is certain that the primary cause of cardiorenal syndrome is the kidney disease. In this paper, we will briefly review the epidemiology of ADPKD, conventional and novel biomarkers which may be useful in following the disease process, and prevention and treatment strategies