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In order to investigate the behaviour of worm drives, a new dynamic model, composed of two blocks, is established and used to extract numerical results. The tooth deflection of the worm drive, bearings, and wheels inertias are taken into consideration. Newmark solving method is applied to solve motion equations. The state of contact of teeth is what enables these signals to manifest themselves. Modal analysis is developed to investigate the different natural modes of the model. Furthermore, modal energetic analysis is used to understand the distribution of strain and kinetic energies. It is also applied to classify natural models into “teeth modes” and “bearing modes”. These two modes constitute two different frequency bands. The dynamic coefficient is measured simultaneously with the gradual increase of the turning speed of the motor. This allows for the evaluation of the overload of the system.

The prediction of the behavior of vibration isolators is essential for effective and efficient design of these devices, as well as for accurately characterizing the isolator behavior. In this work, an experimental study was performed to characterize the behavior of metal-mesh isolators. Although these elements' performance is of great interest because of their usage in several applications, their characterization is complex due to their nonlinear nature, among other factors. This study's aim was to obtain the quasi-static behavior of these isolators, although dynamic tests are required for their complete characterization. These quasi-static tests allowed for the highlighting of some characteristics in a simpler and faster manner and also provided a starting point for designing future dynamic tests. The quasi-static tests performed resulted in the calculation of the hysteresis cycle under different operating conditions and manufacturing parameters. The study of different insulator characteristics, such as the energy dissipation coefficient and stiffness, led to interesting conclusions about the isolator performance. From the results, it was observed that the relative density affected most the nonlinear behavior of the insulator. Moreover, to correctly characterize their behavior, not only the Coulomb's damping but also the viscous damping had to be considered. [ABSTRACT FROM AUTHOR]

Background: Worm gear sets are used in many applications of the transmission field. These mechanisms have interesting advantages. Despite this, its modelization is still challenging. This is due to its complex geometry. The goal behind this is to have an accurate model that allows improvement of the design of worm gear sets. Purpose: In this context, the paper presents a new mathematical model of a worm gear drive under rotational external excitations. Methods: Dynamic model is defined by fourteen degrees of freedom describing all rotations and translations of worm gear set, AQ1 bearings, a motor and a receiver connected together. First, equations of motion are developed to describe the dynamic behavior. Lagrange formula is, thus, employed. Elastic deformations of meshed teeth are considered. The normal load associated with the meshing is established as function of the model degrees of freedom through the elastic deflection. Second, a numerical simulation is carried out. Newmark Beta method is used to solve equations. Results: Numerical results are presented to discuss the model accuracy. The impact of the variation of friction coefficient and the stiffness of the worm gear is finally studied to discuss the consistency of the new formulation developed through this work. [ABSTRACT FROM AUTHOR]

Simple Summary: This is a collaborative approach between two multicentre structures, the Spanish Group of Ovarian Cancer Research (GEICO) and the Spanish Biobank Network (RNBB), for collecting high-quality clinical data and associated biospecimens from gynaecological patients in the context of a virtual clinical registry (VCR). The model described herein defines the mode of operation of this initiative and represents a win-win example between multicentre structures that will contribute to the success of translational research in gynaecological cancer. As of December 2021, 30 active sites have recruited a total of 655 patients in the GEICO VCR, distributed in the following cohorts: Ovarian Cancer (377), Endometrial Cancer (206), Cervical Cancer (67), and Rare Tumours (5). The main type of associated biospecimens are formalin-fixed and paraffin-embedded tissue, plasma, serum, and buffy-coat. Patient registries linked to biorepositories constitute a valuable asset for clinical and translational research in oncology. The Spanish Group of Ovarian Cancer Research (GEICO), in collaboration with the Spanish Biobank Network (RNBB), has developed a multicentre, multistakeholder, prospective virtual clinical registry (VCR) associated with biobanks for the collection of real-world data and biological samples of gynaecological cancer patients. This collaborative project aims to promote research by providing broad access to high-quality clinical data and biospecimens for future research according to the needs of investigators and to increase diagnostic and therapeutic opportunities for gynaecological cancer patients in Spain. The VCR will include the participation of more than 60 Spanish hospitals entering relevant clinical information in harmonised electronic case report forms (eCRFs) in four different cohorts: ovarian, endometrial, cervical, and rare gynaecological cancers (gestational trophoblastic disease). Initial data for the cases included till December 2021 are presented. The model described herein establishes a real-world win-win collaboration between multicentre structures, promoted and supported by GEICO, that will contribute to the success of translational research in gynaecological cancer. [ABSTRACT FROM AUTHOR]

Predictive biomarkers of trabectedin represent an unmet need in advanced soft‐tissue sarcomas (STS). DNA damage repair (DDR) genes, involved in homologous recombination or nucleotide excision repair, had been previously described as biomarkers of trabectedin resistance or sensitivity, respectively. The majority of these studies only focused on specific factors (ERCC1, ERCC5, and BRCA1) and did not evaluate several other DDR‐related genes that could have a relevant role for trabectedin efficacy. In this retrospective translational study, 118 genes involved in DDR were evaluated to determine, by transcriptomics, a predictive gene signature of trabectedin efficacy. A six‐gene predictive signature of trabectedin efficacy was built in a series of 139 tumor samples from patients with advanced STS. Patients in the high‐risk gene signature group showed a significantly worse progression‐free survival compared with patients in the low‐risk group (2.1 vs 6.0 months, respectively). Differential gene expression analysis defined new potential predictive biomarkers of trabectedin sensitivity (PARP3 and CCNH) or resistance (DNAJB11 and PARP1). Our study identified a new gene signature that significantly predicts patients with higher probability to respond to treatment with trabectedin. Targeting some genes of this signature emerges as a potential strategy to enhance trabectedin efficacy. [ABSTRACT FROM AUTHOR]

Objective: The aim of this survey conducted by 20 leading Spanish oncologists was to analyze the concurrence between Spanish clinical practice and the recently published definition of the optimal sequence for the systemic treatment of metastatic breast cancer (MBC) according to patient profiles. Methods: A self-administered questionnaire was developed, divided into five sections comprising 34 specific questions related to sequential treatments, plus three additional general questions. Respondents were asked to justify negative answers. Participants were recruited randomly by invitation out of a total of 619 oncologists. The questionnaire was sent and collected via e-mail between October 2015 and May 2016. A total of 191 completed questionnaires were received. Results: Overall, 70% of oncologists would keep the three patient profiles exactly as proposed (hormone receptor-positive and HER2-negative, HER2-positive, and triple negative breast cancer). Affirmative answers to questions regarding treatment sequences for these patient profiles (1–34) ranged from 77.8–99.5%, with an average of 90.9% of oncologists being in agreement with the recommended sequential treatments. The lowest degree of consensus was observed for endocrine treatments in pre-menopausal women and for chemotherapy options in hormone-resistant patients, whilst the highest degree of consensus was reached for targeted therapies in HER2-positive patients and for endocrine therapy in post-menopausal women. In their comments, participants revealed a number of economic constraints that prevented them from implementing some of the best treatment options. Conclusions: In conclusion, despite the complexity of MBC treatment, there is general agreement on the optimal treatment sequences. [ABSTRACT FROM AUTHOR]

Background: Reference centers (RCs) are a key point for improving the survival of patients with soft‐tissue sarcomas (STS). The aim of this study was to evaluate selected items in the management of patients with STS, comparing results between RC and local hospitals (LHs). Materials and Methods: Diagnostic and therapeutic data from patients diagnosed between January 2004 and December 2011 were collected. Correlation with outcome was performed. Results: A total of 622 sarcomas were analyzed, with a median follow‐up of 40 months. Imaging of primary tumor preoperatively (yes vs. no) correlated with a higher probability of free surgical margins (77.4% versus 53.7%; p =.006). The provenance of the biopsy (RC vs. LH) significantly affected relapse‐free survival (RFS; 3‐year RFS 66% vs. 46%, respectively; p =.019). Likewise, 3‐year RFS was significantly worse in cases with infiltrated (55.6%) or unknown (43.4%) microscopic surgical margins compared with free margins (63.6%; p <.001). Patients managed by RCs had a better 3‐year overall survival compared with those managed by LHs (82% vs. 70.4%, respectively; p =.003). Perioperative chemotherapy in high‐risk STS, more frequently administered in RCs than in LHs, resulted in significantly better 3‐year RFS (66% vs. 44%; p =.011). In addition, patients with stage IV disease treated in RCs survived significantly longer compared with those in LHs (30.4 months vs. 18.5 months; p =.036). Conclusion: Our series indicate that selected quality‐of‐care items were accomplished better by RCs over LHs, all with significant prognostic value in patients with STS. Early referral to an RC should be mandatory if the aim is to improve the survival of patients with STS. Implications for Practice: This prospective study in patients diagnosed with soft‐tissue sarcoma shows the prognostic impact of reference centers in the management of these patients. The magnitude of this impact encompasses all steps of the process, from the initial management (performing diagnostic biopsy) to the advanced disease setting. This is the first prospective evidence showing improvement in outcomes of patients with metastatic disease when they are managed in centers with expertise. This study provides extra data supporting referral of patients with sarcoma to reference centers. Management of soft‐tissue sarcoma is challenging. This article reports on sarcoma clinical management in cancer centers in Spain, based on information from a prospective registry launched by the Spanish Group for Research in Sarcoma. [ABSTRACT FROM AUTHOR]

This paper proposes using a student design competition as a learning tool in the Mechanical Engineering Degree for enhancing the general competences and motivation of the students, transferring theoretical knowledge to practical situations and bringing together all courses involved under a common framework. This constitutes an added value that the in-person universities should offer to their students as a consequence of the Bologna process and the raising of open online resources for self-learning. In order to assess the viability of this proposal, a pilot competition design activity (CDA) is presented using project-based learning methods during a Mechanism Theory course for sophomore students. Meanwhile, 27 participants of a 45-student course from a European university took part in the pilot CDA, which consisted of redesigning the motorbike rear suspension used in a student design competition. Participants also completed mid-term and final exams as well as a survey to get their perception of this activity. Based on the success of the pilot CDA, the authors are planning to implement the proposal, including similar CDAs in other Mechanical Engineering courses to use the competition as a link between them and to encourage students to participate on the competition. [ABSTRACT FROM AUTHOR]

The article presents the study regarding the treatment of metastatic breast cancer (mBC) through anti-human epidermal growth factor receptor 2 (HER2) therapy.

Despite the progress achieved in the treatment of breast cancer, there are still many unsolved clinical issues, being the diagnosis, prognosis, and treatment of papillary diseases, one of the highest challenges. Because of its unpredictable clinical behavior, treatment of intraductal papilloma has generated a great controversy. Even though considered as a benign lesion, it presents high rate of malignant recurrence. This is the reason why there are clinicians supporting a complete excision of the lesion, while others support an only expectant follow-up. Previous results of our group suggested that procollagen 11 alpha 1 (pro-COL11A1) expression correlates with infiltrating phenotype in breast lesions. We analyzed the correlation between expression of pro-COL11A1 in intraductal papilloma and their risk of malignant recurrence. Immunohistochemistry of pro-COL11A1 was performed in 62 samples of intraductal papilloma. Ten out 11 cases relapsed as carcinoma presents positive staining for COL11A1, while just 17 out of 51 cases with benign behaviour present immunostaining. There were significant differences (P < 0.0001) when comparing patients with malignant recurrence versus nonmalignant relapse patients. These data suggest that pro-COL11A1 expression is a highly sensitive biomarker to predict malignant relapse of intraductal papilloma and it can be used as indicative factor for prevention programs. [ABSTRACT FROM AUTHOR]

The development of vibration-based condition monitoring techniques, especially those focused on prognosis, requires the development of better computational models that enable the simulation of the vibratory behaviour of mechanical systems. Gear transmission vibrations are governed by the so-called gear mesh frequency and its harmonics, due to the variable stiffness of the meshing process. The fundamental frequency will be modulated by the appearance of defects which modify the meshing features. This study introduces an advanced model to assess the consequences of defects such as cracks and pitting on the meshing stiffness and other related parameters such as load transmission error or load sharing ratio. Meshing forces are computed by imposing the compatibility and complementarity conditions, leading to a non-linear equation system with inequality constraints. The calculation of deformations is subdivided into a global and a local type. The former is approached by a finite element model and the latter via a non-linear Herztian-based formulation. This procedure enables a reduced computational effort, in contrast to conventional finite element models with contact elements. The formulation used to include these defects is described in detail and their consequences are assessed by a quasi-static analysis of a transmission example. [ABSTRACT FROM AUTHOR]

This article presents a general method for the dimensional synthesis of mechanisms. This method is based on the well-known Sequential Quadratic-Programming algorithm (SQP). However, several modifications have been introduced in order to improve the robustness and efficiency of the method. One of these modifications in the improved SQP approach is the use of the exact Jacobian instead of the finite differences (FD) methods. The article explains how to obtain the Jacobian for any structural kinematic chain. Furthermore, the method introduces several steps in order to prepare the mechanism for optimization. These steps consist in the translation, rotation, and scaling of the mechanism to be designed. The formulation implemented in the algorithm avoids singular configurations and ensures the assembly of the mechanism providing greater robustness than the conventional approach. In the article, several examples are provided to demonstrate the main characteristics of the method. [ABSTRACT FROM PUBLISHER]

Ovarian cancer causes more deaths than any other gynecologic malignancy in developed countries. Sixteen million sequence variants, identified through whole-genome sequencing of 457 Icelanders, were imputed to 41,675 Icelanders genotyped using SNP chips, as well as to their relatives. Sequence variants were tested for association with ovarian cancer (N of affected individuals = 656). We discovered a rare (0.41% allelic frequency) frameshift mutation, c.2040_2041insTT, in the BRIP1 (FANCJ) gene that confers an increase in ovarian cancer risk (odds ratio (OR) = 8.13, P = 2.8 × 10?14). The mutation was also associated with increased risk of cancer in general and reduced lifespan by 3.6 years. In a Spanish population, another frameshift mutation in BRIP1, c.1702_1703del, was seen in 2 out of 144 subjects with ovarian cancer and 1 out of 1,780 control subjects (P = 0.016). This allele was also associated with breast cancer (seen in 6/927 cases; P = 0.0079). Ovarian tumors from heterozygous carriers of the Icelandic mutation show loss of the wild-type allele, indicating that BRIP1 behaves like a classical tumor suppressor gene in ovarian cancer. [ABSTRACT FROM AUTHOR]

The objective of the study was to assess the feasibility, toxicity, and reasons for early discontinuation of a modified outpatient intraperitoneal/intravenous (IP/IV) chemotherapy regimen for the treatment of patients with optimally debulked stage III ovarian cancer.Between February 2006 and November 2008, 51 consecutive patients from Institutions of the Spanish Ovarian Cancer Group (GEICO) were treated with a modified outpatient IP chemotherapy regimen. Patients received IV paclitaxel 175 mg/m2 over 3 hours on day 1, followed by IP cisplatin 100 mg/m2 (or 75 mg/m2 according to the principal investigator's criteria) on day 2. On day 8, patients received IP paclitaxel 60 mg/m2. To homogenize the IP administration and supportive measures, a GEICO guideline for IP chemotherapy was established. Patients were treated with the intention to receive 6 courses of chemotherapy every 21 days.The median age of the patients was 49 years (range, 36-75 years), and most of them had papillary serous ovarian cancer (78%), International Federation of Gynecology and Obstetrics stage IIIC (76%). Thirty-nine patients completed 4 or more IP cycles, and 28 (61%) completed all 6 IP cycles. Twenty-two patients discontinued the IP/IV treatment, mainly because of chemotherapy toxicity (10 patients) and catheter-related complications (5 patients). The most prevalent grade 3/4 toxicities were neutropenia (14 patients; 30%) and gastrointestinal events (12 patients; 26%).The GEICO outpatient modified regimen resulted in a lesser toxicity and a greater rate of treatment completion than previously reported. The accurate selection of patients and the administration following well-defined guidelines can increase the feasibility of IP chemotherapy administration. [ABSTRACT FROM AUTHOR]

This paper is focused on the kinematic design of double-wishbone suspension systems in vehicles, which is tackled using a multiobjective dimensional synthesis technique. The synthesis goal is to optimise an RSSR-SS linkage, subject to some constraints involved in the dynamic behaviour of vehicles. The synthesis method is based on gradient determination using exact differentiation to obtain the elements in the Jacobian matrix. These characteristics make the method adapt well to the optimum design of vehicle suspension systems. The method is capable of handling equality and inequality constraints, thus, the usual ranges of values may be imposed on the functional parameters. The formulation presented is easy to implement and the solutions obtained demonstrate the accuracy and robustness of the method. [ABSTRACT FROM AUTHOR]

Explores by using experimental methods the major factors that affect tax compliance. Detection and punishment; Burden of taxation; Public good provision; Overweighing of low probabilities; Social norms.

Simple Summary: Soft tissue sarcomas (STS) are an uncommon and heterogeneous group of tumors, with scarce options for treatment in advanced cases. There is no consensus regarding which is the best treatment sequence for these patients. Although trabectedin is an approved drug for STS treatment, after progression to anthracyclines, the clinical profile of the patients that most benefit from this drug it is not defined. We have retrospectively analyzed a sample of 357 nonselected sarcoma patients from real-world experience, treated homogeneously with trabectedin, confirming and validating results from previous clinical trials and other retrospective studies. After analyzing clinical prognostic factors, we selected those which predicted a better growth modulation index (GMI > 1.33), and we defined the GEISTRA score, an easy to obtain and reproducible clinical tool, that can help us to optimize the use of trabectedin in advanced sarcoma patients. The aim of this study was to identify an easily reliable prognostic score that selects the subset of advanced soft tissue sarcoma (ASTS) patients with a higher benefit with trabectedin in terms of time to progression and overall survival. A retrospective series of 357 patients with ASTS treated with trabectedin as second- or further-line in 19 centers across Spain was analyzed. First, it was confirmed that patients with high growth modulation index (GMI > 1.33) were associated with the better clinical outcome. Univariate and multivariate analyses were performed to identify factors associated with a GMI > 1.33. Thus, GEISTRA score was based on metastasis free-interval (MFI ≤ 9.7 months), Karnofsky < 80%, Non L-sarcomas and better response in the previous systemic line. The median GMI was 0.82 (0–69), with 198 patients (55%) with a GMI < 1, 41 (11.5%) with a GMI 1–1.33 and 118 (33.1%) with a GMI > 1.33. The lowest GEISTRA score showed a median of time-to-progression (TTP) and overall survival (OS) of 5.7 and 19.5 months, respectively, whereas it was 1.8 and 3.1 months for TTP and OS, respectively, for the GEISTRA 4 score. This prognostic tool can contribute to better selecting candidates for trabectedin treatment in ASTS. [ABSTRACT FROM AUTHOR]

This study evaluates whether serum phospholipids fatty acids (PL-FAs) and markers of their endogenous metabolism are associated with breast cancer (BC) subtypes. EpiGEICAM is a Spanish multicenter matched case-control study. A lifestyle and food frequency questionnaire was completed by 1017 BC cases and healthy women pairs. Serum PL-FA percentages were measured by gas chromatography-mass spectrometry. Conditional and multinomial logistic regression models were used to quantify the association of PL-FA tertiles with BC risk, overall and by pathological subtype (luminal, HER2+ and triple negative). Stratified analyses by body mass index and menopausal status were also performed. Serum PL-FAs were measured in 795 (78%) pairs. Women with high serum levels of stearic acid (odds ratio (OR)T3vsT1 = 0.44; 95% confidence interval (CI) = 0.30–0.66), linoleic acid (ORT3vsT1 = 0.66; 95% CI = 0.49–0.90) and arachidonic to dihomo-γ-linolenic acid ratio (OR T3vsT1 = 0.64; 95% CI = 0.48–0.84) presented lower BC risk. Participants with high concentrations of palmitoleic acid (ORT3vsT1 = 1.65; 95% CI = 1.20–2.26), trans-ruminant palmitelaidic acid (ORT3vsT1 = 1.51; 95% CI = 1.12–2.02), trans-industrial elaidic acid (ORT3vsT1 = 1.52; 95% CI = 1.14–2.03), and high oleic to stearic acid ratio (ORT3vsT1 = 2.04; 95% CI = 1.45–2.87) showed higher risk. These associations were similar in all BC pathological subtypes. Our results emphasize the importance of analyzing fatty acids individually, as well as the desaturase activity indices. [ABSTRACT FROM AUTHOR]

Accurate diagnosis of invasive breast lesions, when analyzed by Core Needle Biopsy, may suppose a major challenge for the pathologist. Various markers of invasiveness such as laminin, S-100 protein, P63 or calponin have been described; however, none of them is completely reliable. The use of a specific marker of the infiltrating tumor microenvironment seems vital to support the diagnosis of invasive against in situ lesions. At this point, Collagen, type XI, alpha 1 (COL11A1), might be helpful since it has been described to be associated to cancer associated fibroblasts in other tumors such as lung, pancreas or colorectal. This paper aims to analyze the role of COL11A1 as a marker of invasiveness in breast tumor lesions. Two hundred and one breast Core Needle Biopsy samples were analyzed by immunohistochemistry against pro-COL11A1. The results show a significant difference ( p < 0.0001) when comparing the expression in infiltrative tumors (93%) versus immunostaining of non-invasive lesions (4%). Forty cases of underestimated DCIS were also stained for COL11A1, presenting a sensitivity of 90% when compared with p63 and calponin which not tagged invasion. In conclusion, pro-COL11A1 expression is a promising marker of invasive breast lesions, and may be included in immunohistochemical panels aiming at identifying infiltration in problematic breast lesions. [ABSTRACT FROM AUTHOR]