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Given the increasing incidence of thyroid cancer cases affecting the pediatric population in Europe, an epidemiological analysis of the available data is essential in order to update standards of care and recommend diagnostic and therapeutic strategies coherent to the new epidemiological trend. An observational study was conducted, considering the time interval 1991–2012, acquiring data collected by the International Agency for Research on Cancer (IARC) through the “Cancer Incidence in 5 continents plus” (CI5 plus) project and dividing patients into four groups of age (0–4, 5–9, 10–14, 15–19 years old). Data retrieved were compared to the latest report from Global Cancer Observatory, collected through the GLOBOCAN 2020 project, dividing patients in two groups: age 10–14, 15–19. Our findings highlighted an increasing prevalence of thyroid cancer rates in patients aged from 10 to 15 years old and from 15 to 19 years old, mainly in the female population, in Belarus (from 1991 to 2007), Cyprus, and Italy (from 2008 to 2012). Moreover, a further increase in incidence was highlighted in Italy according to data from GLOBOCAN 2020, with respect to other European countries.Conclusion: An increasing prevalence of thyroid cancer is seen in age groups 10–19. Further research is required to understand the underlying cause and concomitantly identify the most proper screening and diagnostic techniques of thyroid nodules. Indeed, this is crucial to reach optimal surgical standards and better prognosis, possibly with more conservative approaches and maybe less postoperative complications. What is Known:• Thyroid cancer is the 4th most common malignancy in children. What is New:• In the last decades, an increasing pattern has been recorded.• In the US, it has outlined breast cancers as the most common cancer in females.

SommarioL’iperparatiroidismo primario si manifesta in forma familiare nel 5% dei casi. L’età di insorgenza e la presentazione clinica di queste forme familiari sono variabili in base alla mutazione genica che sottende la sindrome. Il trattamento chirurgico delle forme familiari di iperparatiroidismo primario differisce in base alla specifica sindrome e rappresenta una sfida chirurgica per l’intrinseco rischio di recidiva/persistenza. Inoltre, l’ottimale strategia chirurgica è spesso dibattuta per la necessità di bilanciare un efficace trattamento con il rischio di complicanze, in particolare l’ipoparatiroidismo definitivo e la paralisi del nervo laringeo ricorrente. Il trattamento chirurgico rimane il trattamento di scelta per tutte le forme familiari di iperparatiroidismo primario riportate nella presente rassegna.

Context Measurement of driver mutations in circulating tumoral DNA (ctDNA) obtained by liquid biopsy has been shown to be a sensitive biomarker in several human tumors. Objective The aim of this study was to evaluate the clinical relevance of pre- and post-operative ctDNA in sporadic medullary thyroid cancer (sMTC). Methods We studied pre- and post-operative ctDNA in 26 and 23 sMTC patients, respectively. ctDNA results were correlated to serum calcitonin (Ct), carcinoembryonic antigen (CEA), and other clinical/pathological features. Results Twenty-six of 29 (89.7%) sMTCs were mutated either for RET or RAS and 3/29 (10.3%) were negative. Four of 26 (15.4%) cases showed positive pre-operative ctDNA with a significantly higher presence of RET M918T mutation (P = 0.0468). Patients with positive pre-operative ctDNA showed a higher variation allele frequency value of the somatic driver mutation (P = 0.0434) and a higher frequency of persistent disease (P = 0.0221). Post-operative ctDNA was positive only in 3/23 (13%) sMTCs and no one was positive for pre-operative ctDNA. Higher values of both Ct (P = 0.0307) and CEA (P = 0.0013) were found in positive ctDNA cases. Finally, the 7 cases harboring either pre- or post-operative positive ctDNA had a persistent disease (P = 0.0005) showing a higher post-operative serum Ct when compared with cases with negative ctDNA (P = 0.0092). Conclusions Pre-operative ctDNA in medullary thyroid cancer is not useful for diagnostic purposes, but it can be useful for predicting the outcome of the disease. In our series, post-operative ctDNA showed a potential for monitoring the response to therapies, but further studies are required to confirm our results.

Sketching is becoming an irrelevant activity of engineering studies. The availability of many software that aids designers in all phases of design, not only analytic but synthetic, push technicians, designers to use such tools, giving up the employment of a simple pencil and eraser on a sheet of paper. The productivity of software tools is obliged to speed and manage the whole design process; even freehand sketching remains the fundamental means to communicate the first ideas immediately. During Brainwriting sessions, the ability to explain by sketches first elaborations of a possible solution, that must be understood by co-designers, is the first step that allows more fruitful discussion and immediate adjustment towards a quick embodiment of valid proposals. The paper describes how such techniques has been introduced in the mechanical engineering curriculum. The case of study reports the experience of the Brainwriting online, which has been tested during lockdown due to the pandemic disease of COVID-19. Further in the paper it is suggested a new interpretation of the de Saussure general linguistic studies, in term of a communication that is associated to a drawing.

Product design is an activity that must be supported by information in order to allow designers to conceive solutions to real problems that do not introduce further issues, first of all, environmental concerns. Axiomatic design is an approach that provides the possibility to check whether a design solution is functionally valid and it can also be extended considering eco-design elements. In a synthetic representation of 1D and 2D arrays, it can inform designers about the level of sustainability of the product on which they have been working on since the first phase of design when they start to embody functionalities by introducing real components, and first assemblies appear. To achieve this task, the domains considered in the original formulation of Axiomatic Design have been revised, and a new domain has been introduced. This allows designers to take into account all the phases of product life and improve design solutions to avoid introducing structures, components, and functionalities that might be the cause of environmental problems. The paper describes such new mapping among domains and applies it to design a daily life device. The contents of the new data structure will be presented and discussed.

In the last years, the precision and personalized medicine is pushing the biomedical research efforts towards the direction of implant surgery requiring only 1-step approach: this goal has been achieved after the introduction of resorbable implants. The resorbable prosthetic support is indicated for temporary prosthetic applications, such as bone fractures fixation, or all those conditions usually treated with metal implants then removed with a second surgery, just after the healing of the bone defect. Biodegradable, bioactive and customizable implants for the treatment of bone fractures, both efficient in bearing the functional loads, and showing good biocompatibility and degradation properties matching the bone tissue healing, are still lacking. These premises have led to consider Magnesium (Mg) and its alloys as very promising candidates for the development of temporary, resorbable implants. However, the very high corrosion rate of Mg is the main problem, not yet solved. The material needs to be properly treated/coated, as well as manufactured, in order to design the most suitable duration of the temporary prosthesis permanence in situ. An innovative and interdisciplinary approach has been developed within the M.Era-Net ISIDE project and it is here briefly detailed with a special focus on the highlighted application fields.

Postoperative hypocalcemia is a frequent complication after thyroidectomy. Hypoparathyroidism may develop as transient (TtHP), with normalization within six months from surgery, or permanent (PtHP) if the patient requires replacement therapy. We analyzed factors associated with the development of postoperative hypoparathyroidism and in detail PtHP following thyroid surgery in a pediatric population.A retrospective multicenter study analyzing 326 patients was carried out. We recorded gender, age, tumor size, thyroiditis, extrathyroidal extension, lymph node dissection (central/lateral compartment, unilateral/bilateral), parathyroid autotransplantation, and histology. Additionally, calcium levels were acquired postoperatively.We analyzed pediatric patients ≤18 years who underwent thyroidectomy clustered into age groups (≤15 or 15). Patients' mean follow-up was 5.8 years (1-11 years). Postoperative hypoparathyroidism occurred in 36 (11.0%): 20 cases (6.13%) developed PtHP. Postoperative hypoparathyroidism was more frequent in younger patients (P = 0.014), in larger tumors (P 0.001), in case of extrathyroidal extension (P = 0.037), and in central compartment (P = 0.020) and bilateral lymph node dissection (P = 0.030). PtHP was more frequent in older patients (P = 0.014), in case of thyroiditis (P 0.001), and extrathyroidal extension (P 0.001). Concerning the first postoperative calcium level measurement, in the postoperative hypoparathyroidism group, we registered a 8.17 mg/dL value with 14% pre/postoperative decrease (ΔThe risk of postoperative hypoparathyroidism is related to younger age, tumor size, central compartment and bilateral lymph node dissection, extrathyroidal extension, and decrease in postoperative calcium levels. The risk of PtHP is related to older age, thyroiditis, extrathyroidal extension, and decrease in postoperative calcium levels.

Energy-based devices are surgical devices increasingly utilized for thyroid surgery, owing to a reduction of operative time and surgical related complications. The aim of the study is to evaluate whether the use of energy-based devices could improve the complication rate in pediatric thyroid surgery.This is a retrospective observational study. We identified 177 consecutive pediatric patients (Group A) with thyroid diseases, surgically treated by energy-based devices and 237 patients (Group B) treated by conventional clamp and tie technique and matched for sex, age and indication for surgery. Transient and permanent complications rate, operative time and length of hospital stay were compared between the two groups.Patients of Group A experienced a lower complication rate compared to Group B. Particularly, transient (11.3 vs. 19% p 0.05) and permanent post operative hypoparathyroidism (1.7 vs. 5.5%, p 0.05) were lower in Group A. Moreover, operative time was also shorter in Group A compared to Group B and this difference was statistically significant in patients who performed total thyroidectomy alone and total thyroidectomy associated with central compartment neck dissection (p 0.05). Length of hospital stay was lower in Group A than in Group B, but this difference was statistically significant only for microfollicular lesion (p 0.05).The use of energy-based devices has a key role in reducing surgical related complications, particularly transient and permanent hypoparathyroidism, operative time and length of hospital stay in pediatric patients treated with thyroid surgery.Level III.Retrospective comparative study.

Background: Postoperative hypocalcemia is a frequent complication after thyroid surgery. Hypoparathyroidism may develop as transient (TtHP), with normalization within six months from surgery, or permanent (PtHP) if the patient requires replacement therapy. The present study analyzes rates and factors associated with the development of TtHP or PtHP following thyroid surgery in a pediatric population. Procedure: A retrospective multicenter study analyzing 363 patients was carried out. We recorded gender, age, tumor size, type of surgery, lymph node dissection, histology. Calcium levels were acquired daily for 72 hours after discharge. Subsequent sample collection was customized on the patient’s hypocalcemia severity. Results: We analyzed 363 patients aged ≤18 years (mean age 14.2 years) who underwent thyroid surgery clustered into age groups (≤15 or >15). Patients mean follow-up was 5.8 years (1-11yrs). At histology 310 (85%) were papillary carcinoma, 32 (9%) were follicular carcinoma, 6 (2%) presented diffuse sclerosing variant of papillary thyroid carcinoma whilst 15 (4%) had familial medullary carcinoma. TtHP developed in 36 (9,9%), PtHP in 20 (5.5%) cases. TtHP was more frequent in younger patients (p=0,009). Both PtHP and TtHP were increased in case of larger tumors (≥2 cm) (p=0,001). All TtHP and PtHP were in TT group. PtHP rate was increased if lymph node dissection was carried out (p

Underwater manipulation is a key technology for marine industries and exploration that can be efficiently adopted in other application fields, such as underwater archaeology, biological manipulation, scientific expedition, as well as offshore construction in the Oil and Gas industry. It is performed remotely by expert pilots thanks to the visual feedbacks provided by one or more cameras but without any information about the distance between the end-effector and the target. To this end, the paper presents a novel system based on a sensorized robotic arm, stereoscopic 3D perception and augmented reality visualization to support ROV's pilots in underwater manipulation tasks. The system, thanks to the adoption of an optical-stereo camera, provides a visual feedback of the underwater scene on which a depth map of the underwater workspace is augmented on. In particular, combining the kinematics of the robotic arm and the standard photogrammetric model of the stereo camera, it is possible to generate a depth map that shows to the pilots the distances of the surface of the scene objects from the end-effector's pose. Experimental tests carried out in the context of the CoMAS (In-situ conservation planning of Underwater Archaeological Artefacts) project have demonstrated the effectiveness of the proposed system.

Sporadic medullary thyroid carcinoma (MTC) is a rare malignancy with a heterogeneous clinical course. Several potential prognostic factors have been investigated, but the impact of some of these is controversial, such as age at diagnosis. We evaluated the data of 432 sporadic MTC patients followed-up for a median of 7.4 years. Patients were divided and compared according to their age at diagnosis in group A (&lt, 65 years&mdash, n = 338, 78.2%) and group B (&ge, n = 94, 21.8%). No differences were detected between the two groups. Median follow-up time was significantly longer in patients &lt, 65 than &ge, 65 years. We observed 41 (9.5%) cancer-related death events. The death rate was similar between the two age groups. However, the Kaplan Meier curve showed a longer survival time for younger patients compared to older patients [HR 2.5 (CI 95%: 1.27&ndash, 4.94), p &lt, 0.01]. Nevertheless, no differences in the aggressiveness of the disease at presentation and in the number and type of treatments performed were found in the two subgroups of dead patients. In patients with sporadic MTC, age at diagnosis did not correlate with any clinical and pathological features. Cancer-related death events are similar in older and younger patients, but survival time is longer in the younger.

Teaching product design is not a trivisal task. Considering the experience done along 20 years of teaching at master level class in mechanical engineering it is possible to take stock. The model followed is Project-Based Learning and this method can be licensed as the model that gives greater satisfaction to all attendees. Students give high score to the survey organized by university at the end of the course to assess didactic validity. Also, teachers have many stimuli when discussing with students the activities proposed. The course is based on the development of an industrial product that solves a problem, eventually posed by industry or emerged by customers. Based on the course schedule, the different phases of product development put in evidence the steps that require divergent thinking and those where it is necessary to employ convergent thinking. A case study allows explaining all the phases of product design.

Pandemic Covid19 emergency speeds up universities towards the adoption of Learning Management Systems in order to avoid the physical interaction of students and teachers. Several are the software platforms able to build virtual classes in which the relationship between people is mediated by the web. In the specific case of teaching Machine Drawing, the organization of the course syllabus creates a lot of problems because three types of conjoint activities must be scheduled: lectures, laboratory, and tutoring. Lectures are typically made as one-many relations, also performed online. Really teachers explain the arguments with little interaction with the audience. Tutoring is a one-one relation, in which every student has the opportunity to ask for clarification on not understood or misunderstood topics. Laboratory is the moment in which the hands-on learning activity is performed and when there is the knowledge transfer of all significant topics related to machine drawing and design. How to think about an architectural arrangement of components to reach a design solution for an engineering problem. This last one is really problematic if it is not done by in-person meetings. In fact, generally, it is performed in class with many tables with many students around them and with teachers that exchange information with single or many persons. It must be considered that the initial part of the course Machine Drawing consists of the recall or the first time in which students must draft geometric forms, even by CAD or by hand tools. The authors became to employ Microsoft Teams to manage the virtual class with all activities performed online. The paper describes all the changes made to the course schedule and the way in which Laboratory is performed. In order to not lose the hand nature of most of the activities, the hardware setup is blackboard-friendly. The teacher uses a lot of handwriting, both on a sheet of paper and on the blackboard and the webcams are positioned in such a way that students, online, follow the instructions from a point of view very similar to that of the teacher. Much of the work consists of reviewing the assignments and this is also done online inevitably, working either on scans of the drawings produced by the students using the graphics tablet and suitable software or by showing live the way to solve a drawing problem. All the Laboratory events are recorded for offline learning activities. The exam can only be accessed if the assigned tasks have been completed and verified offline, step by step, by the teacher. The new course organization will be compared with the old one either by assessing the quality of the results of assignments, and by interviewing students, and assessing the result of exams.

Background: Minimally invasive video-assisted thyroidectomy (MIVAT) was first described in 1999 and it has become a widespread technique performed worldwide. Although initially limited to benign thyroid nodules, MIVAT was progressively adopted for all types of thyroid diseases, while remaining within the selection criteria. It is reported that, in selected cases, MIVAT is comparable to standard open thyroidectomy (SOT) in terms of oncologic radicality, time, costs and complications rate, with the advantage of a better cosmetic result and a lower post-operative pain. Methods: The authors conducted a retrospective analysis about patients who underwent MIVAT between 1998 and 2019 in the Endocrine Surgery Unit of the University Hospital in Pisa. Indications and contraindications are mentioned and strictly followed. Results: Total thyroidectomy was performed in 1,862 cases (69%) and hemithyroidectomy was performed in 763 cases (28.3%). Conversion occurred in 43 cases (1.6%). In 188 cases (7%) a postoperative transient hypoparathyroidism was reported, whereas definitive hypoparathyroidism was reported in 12 cases (0.4%). Thirty-eight patients (1.4%) suffered from a definitive postoperative recurrent laryngeal nerve palsy. No definitive bilateral recurrent laryngeal nerve palsy occurred. Conclusions: From our multi-years’ experience which spreads over 20 years, we can reaffirm the concept that MIVAT is a safe procedure which is not burdened by an increase complications rate or additional costs. Furthermore, this technique offers advantages in terms of cosmetic results and post-operative pain.

Prophylactic central compartment lymph node dissection (pCCND) results in a higher percentage of surgical-related complications. To date, no evidence of the impact of pCCND on the clinical outcome of papillary thyroid carcinoma (PTC) patients with synchronous ipsilateral cervical lymph node metastases has been reported.We evaluated all consecutive patients affected by PTC and synchronous ipsilateral cervical, but without evidence of central compartment, lymph node metastases. We selected 54 consecutive patients (group A) treated by total thyroidectomy, ipsilateral cervical lymph node dissection, and pCCND and 115 patients (group B) matched for sex, age at diagnosis, number and dimension of the metastatic lateral cervical lymph nodes, without pCCND. Clinical outcome after a median of 5 years and surgical-related complications were assessed.The two groups were completely similar in terms of clinical features. Clinical outcomes showed a higher percentage of biochemical and indeterminate but not structural response in group B. Group B required significantly more radioiodine treatments, but no difference was shown in the need to repeat surgery for recurrences. Conversely, the prevalence of permanent hypoparathyroidism was significantly higher in group A (14.8%) than in group B (4.3%).In PTC patients with synchronous ipsilateral cervical lymph node metastases, in absence of clinically evident lymph node metastases of the central compartment, performing pCCND does not improve the 5-year outcome in terms of structural disease, despite a greater number ofIQR = interquartile range; pCCND = prophylactic central compartment lymph node dissection; PTC = papillary thyroid carcinoma; Tg = thyroglobulin; US = ultrasound.

The paper discusses the process that leads to choosing a modular building system and how this has suggested a framework to make the right decision in clarifying the task and in generating and selecting new concepts. After illustrating the genesis of the need to build in a modular way, attention shifts to the criteria for evaluating the characteristics of modular buildings. The evaluation criteria were identified and sorted by category and, after an assessment of what already exists on the market and in literature, the guidelines for the design of a new modular building system were provided. The paper also illustrates some conceptual solutions that have arisen from the application of the identified criteria.

The Taguchi method is widely employed in several fields to manage and improve processes. It is interesting that it could be used during product development, considering it as the basic element to quantify the uncertainty of the device performance prediction. During product design, when many design aspects still must be understood by the design team, it is necessary to apply interactive approaches in order to simulate the behaviour of the device, employing CAx tools. Basically it is important to identify the most suitable “loss function” that can be associated with the characteristic function. In order to plane the investigation, the device under development ought to be described in term of the Design Matrix of Axiomatic Design, allowing the designer to characterize the relationship among the functional requirements and the corresponding design parameters. The nature of this relationship, generally not known a priori, can be revealed by the employment of the Taguchi method, once a suitable Objective Function has been chosen and the noise factors are identified. Analysing the performance of a device in a simulation of its behaviour in several operational conditions allows designers to discover whether there are correspondences or contradictions among design parameters. This can be synthetically said a robust design process. In order to enhance these aspects a design of experiment must be planned. The weak point of the procedure consists in the correct choice of the function that characterizes the device behaviour. Considering the wide academic debate on this point, the paper proposes a unique Noise Reduction function to be used in conjunction with all types of “loss function”. The Design Matrix can be checked and its nature can suggest the validity of the product under development and discover contradiction. The paper discusses an interactive procedure able to integrate the Taguchi method and the axiomatic approach.

The paper presents a description of a methodology to accurately estimate the natural frequencies of a hybrid metal-composite gear, where the web is made of a polymer matrix reinforced with two-dimensional (2D) triaxial braided fabrics. The proposed approach is based on a multi-scale composite modeling starting from evaluation of homogenized material properties of the gear web at the meso-scale for a subsequent FE-based modal analysis. For this purpose, the mechanical behavior of a single Repetitive Unit Cell (RUC) at the meso-scale is analyzed with a FE procedure which takes into account the interweaving and cross-section geometry of the yarns, volume fraction and local fiber orientation. It is shown that the described modeling strategy allows to predict gear’s natural frequencies that are close to the experimental results. Significant accuracy enhancement is achieved with respect to the model in which the web material is considered as perfectly isotropic.

Post-thyroidectomy neck hematoma represents a major concern for surgeons because it can result in severe and even life-threatening complications. In fact, postoperative hemorrhage may result in airway compression and respiratory distress, and therefore, effective hemostasis is an important goal in thyroid surgery. Postoperative hematoma occurs at a rate of approximately 0.1% to 1.1%. Almost all cases occur in the first 6 h after surgery and can be the result of several surgeon or patient factors. For many years the clamp-and-tie technique has been the most common way to divide the main vascular pedicles of the thyroid gland. Alternatively, bipolar electrocautery has been used for only very small vessels. Other hemostatic systems have been introduced and proved to be potentially very useful in neck surgery and, in particular, for thyroid surgery. This new class of instruments is generally known as “energy devices” because they use different forms of energy, such as advanced bipolar (LigaSureTM Small Jaw Medtronic, Covidien product, Mineapolis, MN, USA) and ultrasound (Harmonic Focus; Ethicon, Johnson and Johnson, Cincinnati, OH, USA), and hybrid devices that join these two technologies (Thunderbeat by Olympus, Japan). Although they all generate a significant elevation of temperature in the tissues, as in any form of energy, the temperatures reached by these instruments are never as high as the standard monopolar electrocautery. For small bleeding very close to critical structures, where energy devices are too dangerous to be used and clamp and tie is not possible, several studies have assessed the use of adjunctive hemostatic agents. In conclusion, all energy devices have been shown to significantly decrease operative times without increasing costs or complications. Adjunctive hemostatic agents have shown equivalent differences when added to standard methods from a clinically significant perspective.

Purpose To evaluate the efficacy and safety of radiofrequency (RF) ablation in the treatment of benign thyroid nodules (BTNs) by applying a modification of the moving-shot technique. Materials and Methods Fifty-one BTNs in 46 patients for whom surgery was contraindicated or who refused surgery were treated with RF ablation: 31 had lesion volumes 3 (group A) and 20 had volumes ≥ 20 cm 3 (group B). The solid component percentage of each lesion was assessed, and any present fluid component was aspirated. Symptomatic scores and cosmetic scores (CSs) were assessed. All RF ablations were performed under ultrasound (US) guidance with an 18-gauge electrode. Treatment response was evaluated by contrast-enhanced US at 6-month intervals for 18 months in group A. In group B, after the 6- and 12-month follow-up assessments, a second treatment was performed in selected cases, and the 6-month contrast-enhanced US follow-up was started again. Volume reduction rate (VRR) was evaluated at each follow-up examination. Results No permanent paralysis of the laryngeal nerve was observed; 2 patients experienced transient hoarseness. In all nodules treated with a single RF ablation session, the VRRs at 6, 12, and 18 months were 69.4%, 78.7%, and 84% in group A, respectively, and 66.6%, 79.4%, and 81.5% in group B, respectively. The VRRs of group B nodules treated with a second RF ablation procedure (n = 6) were 86.4% and 88.2% at 6 and 12 mo after the second treatment, respectively. All patients reported symptom relief and CS improvement. Conclusions RF ablation is a reliable alternative to surgery in patients affected by BTNs and can be safely repeated in selected cases.

The article presents a model to support designers and stakeholders when selecting the best product concepts, from among those in the course of development, assessing them from the sustainability po...

The first phases of designing an industrial product are those in which creativity has the predominant weight in all the design process. Teaching to be creative is extremely complex and ambiguous, given the elusiveness of the mechanisms that guide it. In this work, the process of generating concepts has been observed during the laboratory of a dyad workgroup of master’s degree students in mechanical engineering in a course of Product Design and Development. Starting from a standard session of the 635 method (Brainwriting) it has been observed how the concepts have evolved in a continuous Brainwriting developed in five steps, between feared and almost manifested moments of fixation and exhaustion, towards increasingly mature and conscious solutions, despite the inexperience of the team members. Some aspects have been highlighted on the rotation mechanism of the different Brainwriting sessions and how this has contributed to concepts development; therefore a framework of a three-step Brainwriting session is proposed, which takes inspiration from this experience and those performed of past years.

ANOVA is currently employed in association with the Robust Design in order to discover the parameters most influencing a particular performance of a device in the phase of development. Such relation has been studied for many times and literature is abundant. The peculiar nature of the Taguchi Method with the employment of orthogonal arrays introduces new elements in the investigation of the most influencing parameters. Considering that the plan of the experiment is organized on the base of level parameters combination orthogonal and balanced, ANOVA can be applied to each parameter individually and this gives new insight on the occurrence of noises in correspondence of some levels parameter. The paper analyses this kind of relation, reproducing an example from literature and discussing how ANOVA can be employed in such a study. Robust Design is an extraordinary method to be used in product development with the experiments simulated from CAE analyses. In this context, more conscious employment of such methodologies can aid in managing and organizing the study and experimentation on new products or processes. In another section a second example from the authors is re-proposed and some new insights are shown.

Background: Autotransplantation of cryopreserved ovarian tissue is currently the main option to preserve fertility for cancer patients. To avoid cancer cell reintroduction at transplantation, a multi-step culture system has been proposed to obtain fully competent oocytes for in vitro fertilization. Current in vitro systems are limited by the low number and health of secondary follicles produced during the first step culture of ovarian tissue fragments. To overcome such limitations, bioreactor designs have been proposed to enhance oxygen supply to the tissue, with inconsistent results. This retrospective study investigates, on theoretical grounds, whether the lack of a rational design of the proposed bioreactors prevented the full exploitation of follicle growth potential. Methods: Models describing oxygen transport in bioreactors and tissue were developed and used to predict oxygen availability inside ovarian tissue in the pertinent literature. Results: The proposed theoretical analysis suggests that a successful outcome is associated with enhanced oxygen availability in the cultured tissue in the considered bioreactor designs. This suggests that a rational approach to bioreactor design for ovarian tissue culture in vitro may help exploit tissue potential to support follicle growth.

The production of prostheses is still not completely optimized, especially for those districts where both functional and aesthetic requirements have to be combined with the urgency of intervention. The prostheses manufactured by machining using CAD/CAM techniques represent the conventional way to obtain a “custom-made” part. However, the above-mentioned solutions are penalized by the too long manufacturing time. This limit can be overcome by using an innovative metal-forming process, i.e. the Incremental Sheet Forming (ISF), which also allows to obtain complex patient-specific geometries even if characterized by a lower precision compared to the conventional process. In this paper, alternative approaches to manufacture a skull prosthesis (i.e. conventional milling and ISF) are compared from technological and economical points of view.

Background Circulating cell-free tumor DNA (ctDNA) in plasma is a promising noninvasive instrument for cancer monitoring. Detection of BRAFV600E on ctDNA of patients with papillary thyroid carcinoma (PTC) may represent an indicator of tumor aggressiveness and progression. Methods Eighty-three plasma samples were collected from 70 patients with thyroid nodules undergoing surgery and from 13 patients with PTC causing distant metastases. A total of 59 PTCs from both groups were evaluated for BRAF mutation on tumor tissue and on ctDNA from plasma samples by real-time polymerase chain reaction (PCR) and digital PCR. Results Of 59 PTCs, 22 were BRAFV600E mutated (37.3%). The corresponding ctDNA was negative by using both techniques. Conclusion Although highly sensitive techniques were used, in our study, circulating BRAFV600E alleles were never detected in the plasma of patients with PTC; therefore, our results raise the question about the clinical usefulness of BRAFV600E analysis on ctDNA of patients with PTC.

Titanium and its alloys are widely used in cranioplasty because they are biocompatible with excellent mechanical properties and favor the osseointegration with the bone. However, when Titanium alloys have to be worked several problems occurred from a manufacturing point of view: the standard procedure for obtaining Titanium prostheses is represented by the machining processes, which result time and cost consuming. The aim of this research consist to introduce alternative flexible sheet forming processes, i.e. Super Plastic Forming (SPF) and Single Point Incremental Forming (SPIF), for the manufacturing of patient-oriented titanium prostheses. The research activities have already highlighted the potentiality of the investigated forming processes that can be alternatively used taking into account both the damage morphology and the need of urgency operation. In the present work, the way of manufacturing the Ti prostheses by SPF and SPIF is described. A comparative analysis has been performed, thus highlighting the peculiarities of the investigated processes and the prostheses feasibility.

The paper discusses the problem of the correct identification of the Objective Function and the associated SNR function that designers must choose when employing the Taguchi method in product design, considering this step as the basic element to quantify the uncertainty of the device performance prediction. During product design, when many design aspects must still be understood by the design team, it is important to identify the most suitable “loss function” that can be associated with the characteristic function. The second step considers the variability of the characteristic function. The Taguchi method considers many Signal to Noise Ratio functions whereas in the paper the use of a unique function is suggested for all kinds of loss function. The discussion is argued in the context of so-called parameter design, with the perspective of identifying the best ranges of variation of the parameters that designers have identified as influential on the characteristic function, and also to adjust those ranges in order to obtain twofold results: reduce Bias between the mean value of the characteristic function response and the target value; obtain less variability of the characteristic function. The discussion of a case of study will point out the approach and the use of a unique Noise Reduction function.

This paper describes a part of the contribution of the CoMAS project (“In situ conservation planning of Underwater Archaeological Artifacts”), funded by the Italian Ministry of Education, Universities and Research (MIUR), and run by a partnership of private companies and public research centers. The CoMAS project aims at the development of new materials, techniques and tools for the documentation, conservation and restoration of underwater archaeological sites in their natural environment. This paper details the results achieved during the project in the development of an innovative electric tool, which can efficiently support the restorers’ work in their activities aimed to preserve the underwater cultural heritage in its original location on the seafloor. In particular, the paper describes the different steps to develop an underwater electric cleaning brush, which is able to perform a first rough cleaning of the submerged archaeological structures by removing the loose deposits and the various marine organisms that reside on their surface. The peculiarity of this work consists in a user centred design approach that tries to overcome the lack of detailed users’ requirements and the lack of norms and guidelines for the ergonomic assessment of such kind of underwater tools. The proposed approach makes a wide use of additive manufacturing techniques for the realization and modification of prototypes to be employed for in-situ experimentation conducted with the final users. The user tests have been addressed to collect data for supporting the iterative development of the prototype.

The present work collects some results of the three-years Research Program “BioForming“, funded by the Italian Ministry of Education (MIUR) and aimed to investigate the possibility of using flexible sheet forming processes, i.e. Super Plastic Forming (SPF) and Single Point Incremental Forming (SPIF), for the manufacturing of patient-oriented titanium prostheses. The prosthetic implants used as case studies were from the skull; in particular, two different Ti alloys and geometries were considered: one to be produced in Ti-Gr23 by SPF and one to be produced in Ti-Gr2 by SPIF. Numerical simulations implementing material behaviours evaluated by characterization tests were conducted in order to design both the manufacturing processes. Subsequently, experimental tests were carried out implementing numerical results in terms of: (i) gas pressure profile able to determine a constant (and optimal) strain rate during the SPF process; (ii) tool path able to avoid rupture during the SPIF process. Post forming characteristics of the prostheses in terms of thickness distributions were measured and compared to data from simulations for validation purposes. A good correlation between numerical and experimental thickness distributions has been obtained; in addition, the possibility of successfully adopting both the SPF and the SPIF processes for the manufacturing of prostheses has been demonstrated.

A new device for the preparation of stoned olive oils, called SPIA, has been developed, aiming at fulfilling the targets of: (i) employing a less powered engine, (ii) reducing the size of the machine and (iii) reaching a good efficiency in terms of oil yields. Oleuropein expression was used as a biochemical parameter to distinguish stoned oils from oils produced by conventional milling systems. In vitro experiments performed by exposing oleuropein to pit enzymes, showed an exponential decay of the substrate.

Background Minimally invasive video-assisted thyroidectomy (MIVAT) proved to be safe and effective in the treatment of both benign and malignant disease. The aim of the present study is to compare MIVAT approach with conventional approach for total thyroidectomy in a group of 99 pediatric patients operated in the Department of General Surgery of the University of Pisa between March 2007 and July 2012. Patients A total of 99 pediatric patients under the age of 18 years with thyroid disease referred to our Department to undergo total thyroidectomy. Patients were divided into two groups according to the surgical technique performed: 34/99 (34.3%) patients (MIVAT group [MG]) and 65/99 (65.7%) patients, (conventional group [CG]) who underwent total thyroidectomy, respectively, with MIVAT approach and conventional approach. Results In MG mean operative time for total thyroidectomy was 40 ± 6.57 minutes (range 30–60 min); postoperative hospital stay was 1 day for 18 patients (53%), 2 days for 12 patients (35.25%), 3 days for 4 patients (11.8%); transient hypoparathyroidism (hypoPTH) was observed in 12 cases (35.3%) and permanent hypoPTH in 2 cases (5.9%); transient postoperative unilateral vocal cord palsy was observed in 2 patients (5.9%). In CG mean operative time for total thyroidectomy was 49.3 ± 12.9 minutes (range 30–80 min); postoperative hospital stay was 1 day for 16 patients (24.6%), 2 days for 40 patients (61.5%), 3 days for 8 patients (12.3%), and 4 days for 1 patient (1.6%); transient hypoPTH was observed in 23 cases (35.4%) and permanent hypoPTH in 4 cases (6.1%), who needed therapy with calcitriol and calcium carbonate; transient postoperative unilateral vocal cord palsy was observed in 4 patients (6.1%). There were no cases of permanent vocal cord paralysis in both groups. The correlation between two groups of patients showed that mean operative time was significantly lower in MG ( p = 0.0007). Conclusion Pediatric patients of MG showed a significantly lower operative time and postoperative hospital stay with respect to pediatric patients of CG if compared with conventional technique. This result with the evidence of similar degree of completeness and rate of postoperative complications make MIVAT a valid option for the treatment of pediatric patients when performed by a well-trained staff in a third referral center.

Patients with amiodarone-induced thyrotoxicosis (AIT) and left ventricular (LV) systolic dysfunction have a high mortality rate. Usually, medical therapy is the first choice for AIT patients, whereas the role of the thyroidectomy is unsettled.The objective of the study was to evaluate the effect of a total thyroidectomy on cardiac function and survival of AIT patients with severe LV systolic dysfunction.This was a retrospective cohort study.The study was conducted at a tertiary university center.All AIT patients (n=24; nine patients with type 1 AIT, 15 patients with type 2 AIT) referred to the Department of Endocrinology and submitted to a total thyroidectomy at the Department of Surgery, both at the University of Pisa, during the years 1997-2010.The intervention was a total thyroidectomy.LV ejection fraction (EF) after the thyroidectomy and survival in December 2011 were measured.All enrolled patients had previously undergone to medical treatment for AIT, as appropriate, without achieving euthyroidism. Patients with moderate to severe LV systolic dysfunction (EF40%, group 1, n=9) or with mild systolic dysfunction (40%≤EF≤50%, group 2, n=5) were compared with patients with normal systolic function (EF50%, group 3, n=10). Two months after thyroidectomy, under levothyroxine replacement therapy, LVEF improved in patients with LV systolic dysfunction, particularly in those of group 1, in whom it increased from 28.2±7.2 to 38.3±6% (P=0.007). On the contrary, LVEF did not significantly change in group 3 (from 57.1±3.0 to 59.8±6.6%, P=0.242). The mean follow-up was 67±42 months. No death occurred during and 2 months after surgery. One death occurred in one patient of group 1, 30 months after the thyroidectomy, due to acute myocardial infarction. No patient had relevant complications of thyroidectomy.Total thyroidectomy, by rapidly restoring euthyroidism, may improve cardiac function and reduce the risk of mortality in AIT patients with severe LV dysfunction.