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Pierachille Santus,1 Fabiano Di Marco,2 Fulvio Braido,3 Marco Contoli,4 Angelo Guido Corsico,5 Claudio Micheletto,6 Girolamo Pelaia,7 Dejan Radovanovic,1 Paola Rogliani,8 Laura Saderi,9 Nicola Scichilone,10 Silvia Tanzi,11 Manlio Vella,11 Silvia Boarino,11 Giovanni Sotgiu,9 Paolo Solidoro12 1Department of Biomedical and Clinical Sciences (DIBIC), Università degli Studi di Milano, Division of Respiratory Diseases, Ospedale L. Sacco, ASST Fatebenefratelli-Sacco, Milano, Italy; 2Department of Health Sciences, Università degli Studi di Milano Pneumology, ASST Papa Giovanni XXIII, Bergamo, Italy; 3Department of Internal Medicine (DiMI), Respiratory Unit for Continuity of Care, IRCCS Ospedale Policlinico San Martino, University of Genova, Genova, Italy; 4Department of Translational Medicine, Respiratory Section, University of Ferrara, Ferrara, Italy; 5Department of Medical Sciences and Infective Diseases, Unit of Respiratory Diseases, IRCCS Policlinico San Matteo Foundation and University of Pavia Medical School, Pavia, Italy; 6Cardio-Thoracic Department, Respiratory Unit, University Integrated Hospital, Verona, Italy; 7Dipartimento di Scienze della Salute, Università Magna Graecia, Catanzaro, Italy; 8Department of Experimental Medicine, Unit of Respiratory Medicine, University of Rome ”Tor Vergata”, Division of Respiratory Medicine, University Hospital ”Tor Vergata”, Rome, Italy; 9Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy; 10Biomedical Department of Internal and Specialist Medicine, University of Palermo, Palermo, Italy; 11AstraZeneca Italia, Milan, Italy; 12Department of Medical Sciences, University of Turin, S.C. Pneumologia, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Torino, ItalyCorrespondence: Pierachille Santus, Università degli Studi di Milano, Via G.B. Grassi 74, Milano, 20157, Italy, Tel +39 0239042801, Fax +39 0239042473, Email pierachille.santus@unimi.itObjective: To describe the burden of moderate to severe exacerbations and all-cause mortality; the secondary objectives were to analyze treatment patterns and changes over follow-up.Design: Observational, multicenter, retrospective, cohort study with a three year follow-up period.Setting: Ten Italian academic secondary- and tertiary-care centers.Participants: Patients with a confirmed diagnosis of COPD referring to the outpatient clinics of the participating centers were retrospectively recruited.Primary and Secondary Outcome Measures: Annualized frequency of moderate and severe exacerbations stratified by exacerbation history prior to study enrollment. Patients were classified according to airflow obstruction, GOLD risk categories, and divided in 4 groups: A = no exacerbations; B = 1 moderate exacerbation; C = 1 severe exacerbation; D = ≥ 2 moderate and/or severe exacerbations. Overall all-cause mortality stratified by age, COPD category, and COPD therapy. A logistic regression model assessed the association of clinical characteristics with mortality.Results: 1111 patients were included (73% males), of which 41.5% had a history of exacerbations. As expected, the proportion of patients experiencing ≥ 1 exacerbation during follow-up increased according to pre-defined study risk categories (B: 79%, C: 84%, D: 97.4%). Overall, by the end of follow-up, 45.5% of patients without a history of exacerbation experienced an exacerbation (31% of which severe), and 13% died. Deceased patients were significantly older, more obstructed and hyperinflated, and more frequently active smokers compared with survivors. Severe exacerbations were more frequent in patients that died (23.5%, vs 10.2%; p-value: 0.002). Chronic heart failure and ischemic heart disease were the only comorbidities associated with a higher odds ratio (OR) for death (OR: 2.2, p-value: 0.001; and OR: 1.9, p-value: 0.007). Treatment patterns were similar in patients that died and survivors.Conclusion: Patients with a low exacerbation risk are exposed to a significant future risk of moderate/severe exacerbations. Real life data confirm the strong association between mortality and cardiovascular comorbidities in COPD.Keywords: pulmonary disease chronic obstructive, heart failure, ischaemic heart disease, respiratory medicine, public health

Background and purposePatients with hereditary hemorrhagic telangiectasia (HHT) have a high prevalence of brain vascular malformations, putting them at risk for brain hemorrhage and other complications. Our aim was to evaluate the relative utility of MR imaging and MRA compared with DSA in detecting cerebral AVMs in the HHT population.Materials and methodsOf 343 consecutive patients evaluated at the University of California, San Francisco HTT Center of Excellence, 63 met the study inclusion criteria: definite or probable hereditary hemorrhagic telangiectasia defined by meeting at least 2 Curacao criteria or positive genetic testing, as well as having at least 1 brain MR imaging and 1 DSA. MRIs were retrospectively reviewed, and the number of AVMs identified was compared with the number of AVMs identified on DSA.ResultsOf 63 patients, 45 (71%) had AVMs on DSA with a total of 92 AVMs identified. Of those, 24 (26%) were seen only on DSA; 68 (74%), on both DSA and MR imaging; and 5 additional lesions were seen only on MR imaging. Of the 92 lesions confirmed on DSA, 49 (53.3%) were seen on the 3D-T1 postgadolinium sequence, 52 (56.5%) were seen on the 2D-T1 postgadolinium sequence, 35 (38.0%) were seen on the SWI sequence, 24 (26.1%) were seen on T2 sequence, and 25 (27.2%) were seen on MRA. The sensitivity and specificity of MR imaging as a whole in detecting AVMs then confirmed on DSA were 80.0% and 94.4%, respectively, and the positive and negative predictive values were 97.3% and 65.4%, respectively.ConclusionsThis study reinforces the use of MR imaging as a primary screening tool for cerebral AVMs in patients with hereditary hemorrhagic telangiectasia and suggests that 3D-T1 postgadolinium and 2D-T1 postgadolinium performed at 3T are the highest yield sequences.

Rationale and Objectives: There are little data as to whether appropriate, cost effective, and safe ordering of imaging examinations are adequately taught in US medical school curricula. We sought to determine the proportion of noninterpretive content (such as appropriate ordering) versus interpretive content (such as reading a chest x-ray) in the top-selling medical student radiology textbooks. Materials and Methods: We performed an online search to identify a ranked list of the six top-selling general radiology textbooks for medical students. Each textbook was reviewed including content in the text, tables, images, figures, appendices, practice questions, question explanations, and glossaries. Individual pages of text and individual images were semiquantitatively scored on a six-level scale as to the percentage of material that was interpretive versus noninterpretive. The predominant imaging modality addressed in each was also recorded. Descriptive statistical analysis was performed. Results: All six books had more interpretive content. On average, 1.4 pages of text focused on interpretation for every one page focused on noninterpretive content. Seventeen images/figures were dedicated to interpretive skills for every one focused on noninterpretive skills. In all books, the largest proportion of text and image content was dedicated to plain films (51.2%), with computed tomography (CT) a distant second (16%). The content on radiographs (3.1:1) and CT (1.6:1) was more interpretive than not. Conclusions: The current six top-selling medical student radiology textbooks contain a preponderance of material teaching image interpretation compared to material teaching noninterpretive skills, such as appropriate imaging examination selection, rational utilization, and patient safety.

Clubfoot is a common birth defect characterized by inward posturing and rigid downward displacement of one or both feet. The etiology of syndromic forms of clubfoot is varied and the causes of isolated clubfoot are not well understood. A microduplication of 2.2 Mb on chromosome 17q23.1q23.2 which includes T-box 4 (TBX4), a hindlimb-specific gene, and 16 other genes was recently identified in 3 of 66 families reported as nonsyndromic clubfoot, but additional non-foot malformations place them in the syndromic clubfoot category. Our study assesses whether variation in or around TBX4 contributes to nonsyndromic clubfoot. To determine whether this microduplication was a common cause of nonsyndromic clubfoot, 605 probands (from 148 multiplex and 457 simplex families) with nonsyndromic clubfoot were evaluated by copy number and oligonucleotide array CGH testing modalities. Only one multiplex family (0.68%) that had 16 with clubfoot and 9 with other foot anomalies, had a 350 kb microduplication, which included the complete duplication of TBX4 and NACA2 and partial duplication of BRIP1. The microduplication was transmitted in an autosomal dominant pattern and all with the microduplication had a range of phenotypes from short wide feet and toes to bilateral clubfoot. Minimal evidence was found for an association between TBX4 and clubfoot and no pathogenic sequence variants were identified in the two known TBX4 hindlimb enhancer elements. Altogether, these results demonstrate that variation in and around the TBX4 gene and the 17q23.1q23.2 microduplication are not a frequent cause of this common orthopedic birth defect and narrows the 17q23.1q23.2 nonsyndromic clubfoot-associated region.

Electron beams of linear induction accelerators experience deflective forces caused by RF fields building up as a result of accelerating cavities of finite size. These forces can significantly effect the beam when a long linac composed of identical cells is assembled. Recent techniques in computational modeling, simulation, and experiments for 20 MeV DARHT-II (Dual Axis Radiographic Hydrodynamic Test) accelerator cells were found to reduce the wakefield impedance of the cells from 800 ohms/meter to 350 ohms/meter and experimental results confirm the results of the modeling efforts. Increased performance of the cell was obtained through a parametric study of the accelerator structure, materials, material tuning, and geometry. As a result of this effort, it was found that thickness-tuned ferrite produced a 50 percent deduction in the wake-field impedance in the low frequency band and was easily tunable based on the material thickness. It was also found that shaped metal sections alloy for high-Q resonances to be de-tuned, thus decreasing the amplitude of the resonance and increasing the cells performance. For the geometries used for this cell, a roughly 45 degree angle had the best performance in affecting the wakefield modes.