Metformin: a modulator of bevacizumab activity in cancer? A case report.

Recurrent type I endometrial cancer ((EC)) has poor prognosis and demands novel therapeutic approaches. Bevacizumab, a VEGF-A neutralizing monoclonal antibody, has shown clinical activity in this setting. To our knowledge, however, although some diabetic cancer patients treated with bevacizumab may also take metformin, whether metformin modulates response to anti-VEGF therapy has not yet been investigated. Here, we report the case of a patient with advanced (EC) treated, among other drugs, with bevacizumab in combination with metformin. The patient affected by relapsed (EC) G3 type 1, presented in march 2010 with liver, lungs and mediastinic metastases. After six cycles of paclitaxel and cisplatin she underwent partial response. Later on, she had disease progression notwithstanding administration of multiple lines of chemotherapy. In march 2013, due to brain metastases with coma, she began steroid therapy with development of secondary diabetes. At this time, administration of Bevacizumab plus Metformin improved her performance status. CT scans performed in this time window showed reduced radiologic density of the lung and mediastinic lesions and of liver disease, suggestive of increased tumor necrosis. Strong F-18-FDG uptake by PET imaging along with high levels of monocarboxylate transporter 4 and lack of liver kinase B1 expression in liver metastasis, highlighted metabolic features previously associated with response to anti-VEGF therapy and phenformin in preclinical models. However, clinical benefit was transitory and was followed by rapid and fatal disease progression. These findingsalbeit limited to a single casesuggest that tumors lacking LKB1 expression and/or endowed with an highly glycolytic phenotype might develop large necrotic areas following combined treatment with metformin plus bevacizumab. As metformin is widely used among diabetes patients as well as in ongoing clinical trials in cancer patients, these results deserve further clinical investigation

Heuristic Learning as a Method for Improving Students’ Teamwork Skills in Physical Education

Transversal skills are the knowledge, skills, and personal qualities that are currently needed to meet the demands of the working world and everyday life. Schools have the task of equipping students with these skills, working not only on disciplinary goals but also on operational–behavioral goals. In 2018, the European Union adopted new recommendations on eight key competencies for lifelong learning and asked schools to implement new methods to develop these recommendations. To be successful, it is necessary to stimulate students’ development of these competences, which are also called soft skills, from the earliest years of the school experience. Physical education (PE) is called upon to make its contribution. In Italy, the two teaching methods used during PE classes are prescriptive teaching and heuristic learning. It is not clear which of the two methods is the most effective in improving soft skills, especially the skills involved in teamwork. The objective of this article was to compare the effects of these two teaching methods on students’ teamwork skills during PE classes in primary schools. After verifying the normality of the data, a Student’s t-test for dependent samples was performed to assess pre-test and post-test differences in each of two groups, while a Student’s t-test for independent samples was performed to compare the two groups after 3 months. Heuristic learning proved to be the most effective method for improving teamwork skills. The results may make an important contribution to future teacher training on the most effective teaching methods for developing students’ soft skill

Dandy-Walker malformation: is the "tail sign" the key sign?

OBJECTIVE.To demonstrate the value of the "tail sign" in the assessment of Dandy-Walker Malformation (DWM). METHODS: A total of 31fetal MRI, performed before 24 weeks of gestation after second-line US examination between May 2013 and September 2014, were examined retrospectively. All MRI examinations were performed using a 1.5 Tesla magnet without maternal sedation. RESULTS: MRI diagnosed 15/31 cases of Dandy-Walker Malformation, 6/31 cases of vermian partial caudal agenesis, 2/31 of vermian hypoplasia, 4/31 of vermian malrotation, 2/31 of Walker-Warburg Syndrome, 1/31 of Blake pouch cyst, 1/31 of rhombencephalosynapsis. All data were compared with fetopsy results, Fetal MR after the 30th week or postnatal MRI; the follow up depended on the maternal decision to terminate or continue pregnancy. In our review study we found the presence of the "tail sign"; this sign was visible only in Dandy-Walker Malformation and Walker-Warburg Syndrome. CONCLUSION: The "tail sign" could be helpful in the difficult differential diagnosis between Dandy Walker, vermian malrotation, vermian hypoplasia and vermian partial agenesis

Sensitivity and representativity analysis of past experiments with respect to ABTR system.

A comprehensive validation analysis has been performed that incorporates representativity of multiple parameters, experiments, reference designs, and adjustment of the nuclear data. The work involves a new representativity study among selected reactor designs and several experiments. Application, using existing experiments, to reference design like the ABTR and the SFR has demonstrated that it is possible to achieve a significant reduction of uncertainty on the main integral parameters of interest for their neutronic design. This is possible when the set of available experiments are relevant (i.e. representative of the reference designs), of good quality (i.e. of reduced uncertainty on experimental results), and consistent (i.e. not providing conflictive information)

Simultaneous Nuclear Data Target Accuracy Study for Innovative Fast Reactors

The present paper summarizes the major outcomes of a study conducted within a Nuclear Energy Agency Working Party on Evaluation Cooperation (NEA WPEC) initiative aiming to investigate data needs for future innovative nuclear systems, to quantify them and to propose a strategy to meet the

Target Accuracy Assessment for an ADS Design

Nuclear data uncertainties and their impact on a very wide range of reactor systems, including their associated fuel cycles, have to be assessed in order to consolidate preliminary design studies for new innovative systems. One specific class of systems is the so-called “dedicated waste transmuters”, that are fast neutron systems (critical or sub-critical, i.e. ADS), loaded with a Minor Actinide (MA) dominated fuel and potentially uranium-free. The availability of very general tools for sensitivity and uncertainty analysis together with new variance-covariance matrix data, produced in a joint effort under the auspices of the OECD-NEA by the world leading nuclear data evaluation groups, makes that endeavor particularly significant. In this report major results of interest for dedicated ADS are discussed and the most important fields and data types are pointed out, where priority improvements are required

Methods in Use for Sensitivity Analysis, Uncertainty Evaluation, and Target Accuracy Assessment

Sensitivity coefficients can be used for different objectives like uncertainty estimates, design optimization, determination of target accuracy requirements, adjustment of input parameters, and evaluations of the representativity of an experiment with respect to a reference design configuration. In this paper the theory, based on the adjoint approach, that is implemented in the ERANOS fast reactor code system is presented along with some unique tools and features related to specific types of problems as is the case for nuclide transmutation, reactivity loss during the cycle, decay heat, neutron source associated to fuel fabrication, and experiment representativity

Prevalence and incidence of bronchiectasis in Italy

BACKGROUND: The understanding of the epidemiology of bronchiectasis is still affected by major limitations with very few data published worldwide. The aim of this study was to estimate the epidemiological burden of bronchiectasis in Italy in the adult population followed-up by primary care physicians. METHODS: This study analyzed data coming from a large primary care database with 1,054,376 subjects in the period of time 2002-2015. Patients with bronchiectasis were selected by the use of International Statistical Classification of Diseases, 9th revision, Clinical Modification codes (ICD-9-CM). RESULTS: Patients with bronchiectasis were more likely to have a history of tuberculosis (0.47% vs. 0.06%, p\u2009<\u20090.0001), had higher rates of asthma (16.6% vs. 6.2%, p\u2009<\u20090.0001), COPD (23.3% vs. 6.4%, p\u2009<\u20090.0001) and rheumatoid arthritis (1.9% vs. 0.8%, p\u2009<\u20090.0001). The prevalence and incidence of bronchiectasis in primary care in Italy in 2015 were 163 per 100,000 population and 16.3 per 100,000 person-years, respectively. Prevalence and incidence increased with age and overall rates were highest in men over 75\u2009years old. Prevalence and incidence computed after the exclusion of patients with a diagnosis of either asthma or COPD is 130 per 100,000 and 11.1 cases per 100,000 person-years, respectively. CONCLUSIONS: Bronchiectasis is not a rare condition in Italian adult population. Further studies are needed to confirm our results and provide a better insight on etiology of bronchiectasis in Italy