Influenza dei criteri di progettazione sull'affidabilità sismica dei controventi concentrici

2008-2009Nell'ottica del Performance Based Seismic Design verifica e progettazione di strutture in zona sismica vanno condotte definendo una serie di stati corrispondenti a situazioni di malfunzionamento e controllando che le strutture possiedano un adeguato livello di protezione nei riguardi del superamento di detti stati. Riconoscendo, tuttavia, la natura probabilistica delle variabili che intervengono nei problemi di ingegneria strutturale (es. entità dei carichi e proprietà meccaniche dei materiali) il livello di protezione strutturale va inteso in termini di probabilità di superamento di un certo stato di malfunzionamento. Risulta pertanto necessario il ricorso a procedure su base probabilistica che consentano di portare in conto tutte le fonti di incertezza nella valutazione delle prestazioni sismiche, quali le incertezze di carattere naturale (connesse alla natura dell'input sismico o record-to record variability) ed epistemologico (connesse alle conoscene limitate). In linea teorica i criteri di progettazione forniti dalle normative dovrebbero condurre al dimensionamento di strutture in grado di esibire un adeguato livello di affidabilità strutturale. Con riferimento ai controventi concentrici, tuttavia, analisi preliminari condotte dal punto di vista deterministico hanno evidenziato un collasso prematuro delle colonne per instabilità fuori piano per le strutture dimensionate secondo gli attuali codici sismici (Eurocodice 8 e Norme Tecniche per le Costruzioni di cui al D.M. 14 gennaio 2008). Tale fenomeno è legato essenzialmente al criterio di progettazione previsto per gli elementi non dissipativi (travi e colonne) che non tiene conto dell'effettiva sovraesistenza delle diagonali. L'obiettivo della tesi è stato quello di analizzare le prestazioni sismiche esibite da controventi dimensionati secondo metodologie di progettazione tradizionali, ossia prescritte dalle vigenti normative in materia di progettazione sismica, ed innovative. In particolare è stata analizzata la metodologia di progettazione a collasso controllato basata sulla rigorosa applicazione dei principi del capacity design. Tale metodologia è finalizzata al dimensionamento di controventi che esibiscano al collasso meccanismi di tipo globale, caratterizzati cioè dalla plasticizzazione di tutte le diagonali tese e dell'instabilizzazione di quelle compresse, allo scopo di conseguire un adeguato livello di duttilità globale. Le prestazioni sismiche delle strutture analizzate sono state valutate dal punto di vista probabilistico. A questo scopo sono stati impiegati: il metodo di Jalayer e Cornell, finalizzato alla stima della frequenza annua media di superamento di un dato stato limite (nell'approccio che considera le sole incertezze di carattere naturale), e le disposizioni delle direttive FEMA 350, finalizzate alla stima del livello di confidenza con il quale una struttura è in grado di esibire le prestazioni connesse ad un dato stato limite (che considerano sia le incertezze di carattere naturale che epistemologico). In aggiunta viene riportato uno studio relativo all'influenza dell'ipotesi di omoschedasticità (dispersione costante della demand al variare della misura dell'intensità dell'azione sismica) nell'approccio di Jalayer e Cornell. I risultati delle analisi di affidabilità hanno evidenziato che le strutture dimensionate secondo normativa esibiscono prestazioni non soddisfacenti, mentre un notevole miglioramento dell'affidabilità sismica può essere conseguito attraverso l'applicazione dell'innovativa metodologia di progettazione a collasso controllato. [a cura dell'autore]VIII n.s

PLASTIC DESIGN OF CB-FRAMES WITH REDUCED SECTION SOLUTION FOR BRACING MEMBERS

The seismic behaviour of concentrically braced frames (CBFs) designed according to the current European provisions is unsatisfactory due to the premature out-of-plane buckling of columns. For this reason, a new design methodology, based on a rigorous application of ``capacity design'' criteria has been recently proposed. In addition, aiming at a reduction of the plastic out of plane deformations of gusset plates due to brace buckling and at the prevention of sudden impact load affecting connections at the end of the straightening phase, Eurocode 8 requires the limitation of the brace slenderness. This limitation leads to the oversizing of diagonals and, consequently, of beams and columns. Therefore, to avoid this problem a new design strategy for bracing members is suggested: the Reduced Section Solution (RSS). It allows the calibration of the diagonal yielding resistance, leaving the brace slenderness practically unchanged. The results of dynamic inelastic analyses carried out with reference to braced frames designed according to the proposed procedure, both with and without RSS, are compared with those obtained with reference to the same structural schemes designed according to Eurocode 8. The obtained results show that the proposed design approaches are able to assure a significant improvement of the seismic performance

Identification of an intragenic deletion in the SGCB gene through a re-evaluation of negative next generation sequencing results

A large mutation screening of 504 patients with muscular dystrophy or myopathy has been performed by next generation sequencing (NGS). Among this cohort of patients, we report a case with a severe form of muscular dystrophy with a proximal weakness in the limb-girdle muscles. Her biopsy revealed typical dystrophic features and immunohistochemistry for α- and γ-sarcoglycans showed an absent reaction, addressing the clinical diagnosis toward a sarcoglycanopathy. Considering that no causative point mutation was detected in any of the four sarcoglycan genes, we re-evaluated the NGS data by careful quantitative analysis of the specific reads mapping on the four sarcoglycan genes. A complete absence of reads from the sixth exon of the β-sarcoglycan gene was found. Subsequent array comparative genomic hybridization (CGH) analysis confirmed the result with the identification of a novel 3.3 kb intragenic deletion in the SGCB gene. This case illustrates the importance of a multidisciplinary approach involving clinicians and molecular geneticists and the need for a careful re-evaluation of NGS data

Congenital myopathy with hanging big toe due to homozygous myopalladin (MYPN) mutation

Background: Myopalladin (MYPN) is a component of the sarcomere that tethers nebulin in skeletal muscle and nebulette in cardiac muscle to alpha-actinin at the Z lines. Autosomal dominant MYPN mutations cause hypertrophic, dilated, or restrictive cardiomyopathy. Autosomal recessive MYPN mutations have been reported in only six families showing a mildly progressive nemaline or cap myopathy with cardiomyopathy in some patients. Case presentation: A consanguineous family with congenital to adult-onset muscle weakness and hanging big toe was reported. Muscle biopsy showed minimal changes with internal nuclei, type 1 fiber predominance, and ultrastructural defects of Z line. Muscle CT imaging showed marked hypodensity of the sartorius bilaterally and MRI scattered abnormal high-intensity areas in the internal tongue muscle and in the posterior cervical muscles. Cardiac involvement was demonstrated by magnetic resonance imaging and late gadolinium enhancement. Whole exome sequencing analysis identified a homozygous loss of function single nucleotide deletion in the exon 11 of the MYPN gene in two siblings. Full-length MYPN protein was undetectable on immunoblotting, and on immunofluorescence, its localization at the Z line was missed. Conclusions: This report extends the phenotypic spectrum of recessive MYPN-related myopathies showing: (1) the two patients had hanging big toe and the oldest one developed spine and hand contractures, none of these signs observed in the previously reported patients, (2) specific ultrastructural changes consisting in Z line fragmentation, but (3) no nemaline or caps on muscle pathology

The position of nonsense mutations can predict the phenotype severity : A survey on the DMD gene

A nonsense mutation adds a premature stop signal that hinders any further translation of a protein-coding gene, usually resulting in a null allele. To investigate the possible exceptions, we used theDMDgene as an ideal model. First, because dystrophin absence causes Duchenne muscular dystrophy (DMD), while its reduction causes Becker muscular dystrophy (BMD). Second, theDMDgene is X-linked and there is no second allele that can interfere in males. Third, databases are accumulating reports on many mutations and phenotypic data. Finally, becauseDMDmutations may have important therapeutic implications. For our study, we analyzed large databases (LOVD, HGMD and ClinVar) and literature and revised critically all data, together with data from our internal patients. We totally collected 2593 patients. Positioning these mutations along the dystrophin transcript, we observed a nonrandom distribution of BMD-associated mutations within selected exons and concluded that the position can be predictive of the phenotype. Nonsense mutations always cause DMD when occurring at any point in fifty-one exons. In the remaining exons, we found milder BMD cases due to early 5' nonsense mutations, if reinitiation can occur, or due to late 3' nonsense when the shortened product retains functionality. In the central part of the gene, all mutations in some in-frame exons, such as in exons 25, 31, 37 and 38 cause BMD, while mutations in exons 30, 32, 34 and 36 cause DMD. This may have important implication in predicting the natural history and the efficacy of therapeutic use of drug-stimulated translational readthrough of premature termination codons, also considering the action of internal natural rescuers. More in general, our survey confirm that a nonsense mutation should be not necessarily classified as a null allele and this should be considered in genetic counselling.Peer reviewe

A novel RAB39B mutation and concurrent de novo NF1 mutation in a boy with neurofibromatosis type 1, intellectual disability, and autism: a case report

Background Mutations in RAB39B at Xq28 causes a rare form of X-linked intellectual disability (ID) and Parkinson’s disease. Neurofibromatosis type 1 (NF1) is caused by heterozygous mutations in NF1 occurring de novo in about 50% of cases, usually due to paternal gonadal mutations. This case report describes clinical and genetic findings in a boy with the occurrence of two distinct causative mutations in NF1 and RAB39B explaining the observed phenotype. Case presentation Here we report a 7-year-old boy with multiple café-au-lait macules (CALMs) and freckling, severe macrocephaly, peculiar facial gestalt, severe ID with absent speech, epilepsy, autistic traits, self-harming, and aggressiveness. Proband is an only child born to a father aged 47. Parents did not present signs of NF1, while a maternal uncle showed severe ID, epilepsy, and tremors.By RNA analysis of NF1, we identified a de novo splicing variant (NM_000267.3:c.6579+2T>C) in proband, which explained NF1 clinical features but not the severe ID, behavioral problems, and aggressiveness. Family history suggested an X-linked condition and massively parallel sequencing of X-exome identified a novel RAB39B mutation (NM_171998.2:c.436_447del) in proband, his mother, and affected maternal uncle, subsequently validated by Sanger sequencing in these and other family members. Conclusions The case presented here highlights how concurrent genetic defects should be considered in NF1 patients when NF1 mutations cannot reasonably explain all the observed clinical features

CHRONIC RHINOSINUSITIS IN CYSTIC FIBROSIS PATIENTS: SMELL EVALUATION

Cystic Fibrosis (CF) involves the upper airways with chronic rhinosinusitis (CRS) causing nasal congestion, rhinorrhea, mouth breathing, facial pain, and olfactory dysfunction. Twelve to 71% of CF patients report smelling alterations impacting nutrition and quality of life. The aim was to study olfaction performance in CF patients with CRS that worsens quality of life. One hundred and twenty-one subjects were enrolled in this study. Seventy-one had CF and underwent ear, nose, and throat evaluation with nasal endoscopy, SNOT-22, VAS and “Sniffin’ Sticks”. Fifty subjects were age-matched with healthy controls. All 71 CF patients were affected by CRS; 59/71 (83.1%) had CRS without nasal polyps and 12/71 (16.9%) had CRS with early nasal polyps. None of the 50 controls had CRS. Total SNOTT-22 mean values in the 71 CF patients was 38.10 ± 21.08 pts. If considering only the 59 CF patients without nasal polyps the SNOTT-22 mean value was 36.76 ± 21.52 pts. Moreover, based on the VAS scores, the degree of nasal symptoms was classified as mild for facial pain, smell alteration, nasal discharge, and sneezing and resulted in moderate symptoms for nasal blockage and headache. Among the CF patients, 55/71 (76.5%) declared normosmia while the smelling ability assessed by “Sniffin’ Sticks” showed that only 4/71 (5.63%) were normosmic, 58 (81.69%) were hyposmic, and 9 (12.68%) were anosmic. In the controls 41(82%) were normosmic, 9 (18%) were hyposmic, and none were reported anosmia (p < 0.001). The study confirms that most CF patients have a relevant olfactory impairment, although only a low percentage declare it. A careful evaluation with simple and rapid tests helps to select the patients that may benefit from specific therapies

Targeted gene panel screening is an effective tool to identify undiagnosed late onset Pompe disease

Mutations in the GAA gene may cause a late onset Pompe disease presenting with proximal weakness without the characteristic muscle pathology, and therefore a test for GAA activity is the first tier analysis in all undiagnosed patients with hyperCKemia and/or limb-girdle muscular weakness. By using MotorPlex, a targeted gene panel for next generation sequencing, we analyzed GAA and other muscle diseasegenes in a large cohort of undiagnosed patients with suspected inherited skeletal muscle disorders (n = 504). In this cohort, 275 patients presented with limb-girdle phenotype and/or an isolated hyperCKemia. Mutational analysis identified GAA mutations in ten patients. Further seven affected relatives were identified by segregation studies. All the patients carried the common GAA mutation c.-32-13T > G and a second, previously reported mutation. In the subcohort of 275 patients with proximal muscle weakness and/or hyperCKemia, we identified late-onset Pompe disease in 10 patients. The clinical overlap between Pompe disease and LGMDs or other skeletal muscle disorders suggests that GAA and the genes causing a metabolic myopathy should be analyzed in all the gene panels used for testing neuromuscular patients. However, enzymatic tests are essential for the interpretation and validation of genetic results. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Failure Mode and Drift Control of MRF-CBF Dual Systems

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