Tip-timing measurements of transient vibrations in mistuned bladed disks

Bladed disks are usually characterized by a rich dynamic response during service due to the occurrence of several mode shapes that vibrate at resonance within the operative range. In particular, during start-ups and shutdowns, the variable speed causes a temporary crossing of resonance that cannot be neglected to determine stress envelope and safety margins of the system during its whole mission. In fact, fluid flow induces fluctuating loads with variable frequencies (non-stationary regime) on the blades being responsible of a dynamic response which does not follow the so-called steady-state (stationary) response. This paper proposes a novel post-processing method for Blade Tip-Timing (BTT) measurements for the identification of the resonance parameters of mistuned bladed disks working in non-stationary operative conditions. The method is based on a two degrees of freedom model (2DOF) and focuses on transient resonances in which two mistuned modes with close resonance frequencies are involved in the dynamic response. In such circumstances, the identification method based on the single degree of freedom (1DOF) model usually fails.To verify the effectiveness of the method, numerical and experimental investigations have been performed. First, a mathematical simulator based on a lumped parameter model of a bladed disk system is used to generate the BTT simulated data. Experimental signals are measured using a commercial BTT system through a set of optical probes mounted circumferentially around a rotating dummy blisk. It is shown that the method produces accurate predictions for the numerical simulation, even in the presence of considerable noise levels. Moreover, experimental results confirm a successful implementation of the method on the actual BTT measurements

adjuvant mitotane for adrenocortical cancer working through uncertainty

The Journal of Clinical Endocrinology & Metabolism recently published a commentary by Huang and Fojo (1) offering a skeptical view on the efficacy of mitotane as an adjunctive postsurgical measure in patients with adrenocortical cancer (ACC). Their commentary focused on outlining the limitations of our recent study which indicated that adjuvant mitotane may prolong recurrence-free survival (RFS) in patients with radically resected ACC (2). However, we do not agree with several of their conclusions and believe that it is of interest to present our view for a balanced and comprehensive coverage of this important matter. Inprinciple,weagreewithHuangandFojothatourstudysuffers from the important limitation of a retrospective analysis; thus our investigation should be considered as hypothesis generating and certainly does not provide conclusive evidence. This problem has been clearly acknowledged in the paper, and we cautiously concluded that our study should renew interest in adjuvant therapy, whereas prospective, randomized trials will be needed to confirm the efficacyof adjuvantmitotane treatment (2).However, the rarity of ACC precluded organization of a randomized trial either in an adjuvantsettingor inpatientswithadvancedACC(3).Nonetheless, mitotane has been used for treating patients with ACC since the 1960s and is the only drug approved for ACC by the U.S. Food and Drug Administration and the European Medicines Evaluation Agency (4). In this scenario, a study including all consecutive patients treated postoperatively with mitotane in some centers and all consecutive patients left untreated after operation in other centers is thebestway toobtainexplorativedataon theefficacyofadjuvant mitotane, provided that the two groups are comparable. In our study, in fact, mitotane was recommended on the basis of the treatmentpolicyof thecenter, independentof thecharacteristicsofeither the tumorsor thepatients, and this is amajoradvantageminimizing selection bias as compared with other studies that had less clear treatment assignments (5). The major criticism of Huang and Fojo (1) is that we did not demonstrate any benefit on overall survival (OS) for patients treated adjuvantly. However, this is not correct because the hazard ratio of death of the German cohort of nontreated patients was nonsignificantly higher than mitotane-treated patients in univariate analysis, but the difference became significant in multivariate analysis after adjusting for imbalances in prognostic factors (the German cohort included more patients with stage I and II ACC than the Italian cohort of mitotane-treated patients). Even when we accept that the effect of adjuvant mitotane on OS was less impressive than on RFS, we disagree that prolonging a disease-free status is not a clinically meaningful objective even without extending significantly duration of life. In addition, there is a long-standing debate on the most appropriate endpoint for adjuvant trials, and both OS and RFS have been suggested. Analysis of RFS has the advantage of needing a shorter follow-up and being directly related to the treatment tested. The most important disadvantage of RFS is its close relationship to the frequency and quality of evaluation. Bias in follow-up or ascertainment of outcome in observational retrospective series is well recognized, and we have acknowledged this potential limit of our study. However, the follow-up procedures were highly comparable among the different centers and included imaging evaluation of the chest and abdomen every 6 months until disease progression or the end of the study period (2). Even if survival has to be considered as the reference end-point, it may not be a direct result of the study drug because it may be strongly influenced by subsequent treatments and oncologists are increasingly considering RFS as a valid surrogate for OS (6). However, this relationship has never been demonstrated specifically in ACC patients. Another criticism is derived from an ill-conceived reanalysis of our data. Huang and Fojo (1) aimed at demonstrating that the time interval between ACC recurrence and death is higher in patients treated adjuvantly than patients left untreated after surgery. Thus, they assumed important differences in tumor biology of the different cohorts. This conclusion comes from subtracting median time to recurrence from median survival observed in th

The dynamic of the apical ectoplasmic specialization between spermatids and sertoli cells : the case of the small GTPase Rap1

Despite advances in assisted reproductive technologies, infertility remains a consistent health problem worldwide. Spermiation is the process through which mature spermatids detach from the supporting Sertoli cells and are released into the tubule lumen. Spermiation failure leads to lack of mature spermatozoa and, if not occasional, could result into azoospermia, major cause of male infertility in human population. Spermatids are led through their differentiation into spermatozoa by the apical ectoplasmic specialization (aES), a testis-specific, actin-based anchoring junction restricted to the Sertoli-spermatid interface. The aES helps spermatid movement across the seminiferous epithelium, promotes spermatid positioning, and prevents the release of immature spermatozoa. To accomplish its functions, aES needs to undergo tightly and timely regulated restructuring. Even if components of aES are partly known, the mechanism/s through which aES is regulated remains still elusive. In this review, we propose a model by which the small GTPase Rap1 could regulate aES assembly/remodelling. The characterization of key players in the dynamic of aES, such as Rap1, could open new possibility to develop prognostic, diagnostic, and therapeutic approaches for male patients under treatment for infertility as well as it could lead to the identification of new target for male contraceptio

L’immagine neutra. Indicazioni e contributi interdisciplinari per la riflessione sull’approccio al design della comunicazione audiovisiva

Nel complesso e dinamico quadro della comunicazione, caratterizzato dal moltiplicarsi dei processi e delle piattaforme comunicative, si assiste ad una estensione del territorio di competenza del linguaggio audiovisivo. Ciò comporta l’ampliarsi sia delle competenze che delle conoscenze del progettista che deve anche relazionarsi con principi di varie discipline e con figure professionali di natura diversa. Il designer, oltre a definire le modalità di fruizione del prodotto e a formalizzare linguaggi visuali, è chiamato a comprendere nuove complessità e a sviluppare, conseguentemente, strategie comunicative alle quali la forma audiovisiva, per la sua efficacia nel veicolare il messaggio, contribuisce in modo sostanziale. La pubblicazione propone una raccolta ragionata di principi ed indicazioni essenziali per orientare verso una cosciente e corretta costruzione del progetto di comunicazione audiovisiva e del suo lessico. La prima parte presenta un panorama multidisciplinare di contributi per la riflessione sul linguaggio per immagini, sulla percezione visiva, sulla comunicazione, sul pensiero sistemico e sull’audiovisivo: una pluralità di punti di vista si rivela funzionale alla definizione del progetto ed alla configurazione del linguaggio audiovisivo ed utile al riconoscimento, da un lato, della loro importanza per l’individuo e la società, dall’altro, della necessità di cogliere l’occasione progettuale di sperimentare nuovi moduli espressivi, nuovi linguaggi, valori e orientamenti per un più equo sviluppo sociale. Ritenendo che la cultura, il linguaggio cinematografico e l’insieme di modalità espressive che il cinema ha sviluppato nel tempo siano saperi fondamentali per operare nell’ambito del design audiovisivo, la seconda parte della pubblicazione si sofferma sulla nascita del cinema e sull’ impiego che l’immagine in movimento ha trovato nel corso della storia, in particolare nella pubblicità e nella propaganda politica. Sono trattate anche le principali regole della grammatica e della sintassi cinematografica, che le nuove forme del prodotto audiovisivo, non esclusa l’autoproduzione, tendono spesso a sottovalutare; sono inoltre descritti alcuni aspetti tecnici per una corretta organizzazione e realizzazione del prodotto cinematografico e quindi dell’ artefatto audiovisivo

Unwanted hormonal and metabolic effects of postoperative adjuvant mitotane treatment for adrenocortical cancer

Mitotane is widely used for the treatment of adrenocortical cancer (ACC), although the drug-related toxicity complicates its use. The aim of this study is to assess comprehensively the different endocrine and metabolic unwanted effects of the drug, and to provide data on the supportive therapies. We retrospectively analyzed 74 ACC patients adjuvantly treated with mitotane for ≥12 months. During the treatment period (40 months, 12–195), 32.4% of patients needed replacement therapy for mineralocorticoid deficit, 36.2% for hypothyroidism and 34.3% for male hypogonadism. In fertile women, hypogonadism was uncommon, while 65.4% of women developed ovarian cysts. Although no significant change in low-density lipoprotein (LDL) was observed, statins were started in 50% of patients for a significant increase in total cholesterol and triglycerides. Dyslipidemia occurred early, after a median time of 6 months from mitotane start. Conversely, testosterone replacement was usually started after >2 years. In many cases, ranging from 29.4% to 50% according to the side effect, toxicity occurred well before the achievement of the target mitotane concentrations. Supportive therapies were able to revert the biochemical alterations induced by mitotane, although higher doses were needed for a likely pharmacokinetic interaction of exogenous steroids and statins with mitotane. In conclusion, adjuvant mitotane therapy is associated with a spectrum of unwanted effects encompassing the function of different endocrine glands and requires a careful clinical and biochemical assessment associated with the therapeutic drug monitoring

Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up F. Pacini, M. G. Castagna, L. Brilli & G. Pentheroudakis On behalf of the ESMO Guidelines Working Group* Section of Endocrinology and Metabolism, Department of Internal Medicine, Endocrinology and Metabolism and Biochemistry, Section of Endocrinology and Metabolism, University of Siena, Siena, Italy; Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greec

Clinical Management of Neuroendocrine Neoplasms in Clinical Practice: A Formal Consensus Exercise

Many treatment approaches are now available for neuroendocrine neoplasms (NENs). While several societies have issued guidelines for diagnosis and treatment of NENs, there are still areas of controversy for which there is limited guidance. Expert opinion can thus be of support where firm recommendations are lacking. A group of experts met to formulate 14 statements relative to diagnosis and treatment of NENs and presented herein. The nominal group and estimate-talk-estimate techniques were used. The statements covered a broad range of topics from tools for diagnosis to follow-up, evaluation of response, treatment efficacy, therapeutic sequence, and watchful waiting. Initial prognostic characterization should be based on clinical information as well as histopathological analysis and morphological and functional imaging. It is also crucial to optimize RLT for patients with a NEN starting from accurate characterization of the patient and disease. Follow-up should be patient/tumor tailored with a shared plan about timing and type of imaging procedures to use to avoid safety issues. It is also stressed that patient-reported outcomes should receive greater attention, and that a multidisciplinary approach should be mandatory. Due to the clinical heterogeneity and relative lack of definitive evidence for NENs, personalization of diagnostic–therapeutic work-up is crucial